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10563 (T > C)

General info

Mitimpact ID
MI.15884
Chr
chrM
Start
10563
Ref
T
Alt
C
Gene symbol
MT-ND4L Extended gene annotation
Gene position
94
Gene start
10470
Gene end
10766
Gene strand
+
Codon substitution
TGC/CGC
AA pos
32
AA ref
C
AA alt
R
Functional effect
missense
OMIM ID
516004
HGVS
NC_012920.1:g.10563T>C
HGNC ID
7460
RC complex
I
Ensembl gene ID
ENSG00000212907
Ensembl protein ID
ENSP00000354728
Ensembl transcript ID
ENST00000361335
Uniprot ID
P03901
Uniprot name
NU4LM_HUMAN
Ncbi gene ID
4539
Ncbi protein ID
YP_003024034.1
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Powered by MitoWheel

Conservation

PhyloP 100v
4.727 Conservation Score
PhyloP 470way
0.666 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.998 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Disease automatic Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Likely-pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
High impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
9706
Clinvar ALLELEID
24745
Clinvar CLNDISDB
Mondo:mondo:0023113, medgen:cn280943
Clinvar CLNDN
Familial colorectal cancer
Clinvar CLNSIG
Pathogenic
MITOMAP Allele
10563T>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
56433
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Npg
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
rs267606892

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

10563 (T > A)

General info

Mitimpact ID
MI.15885
Chr
chrM
Start
10563
Ref
T
Alt
A
Gene symbol
MT-ND4L Extended gene annotation
Gene position
94
Gene start
10470
Gene end
10766
Gene strand
+
Codon substitution
TGC/AGC
AA pos
32
AA ref
C
AA alt
S
Functional effect
missense
OMIM ID
516004
HGVS
NC_012920.1:g.10563T>A
HGNC ID
7460
RC complex
I
Ensembl gene ID
ENSG00000212907
Ensembl protein ID
ENSP00000354728
Ensembl transcript ID
ENST00000361335
Uniprot ID
P03901
Uniprot name
NU4LM_HUMAN
Ncbi gene ID
4539
Ncbi protein ID
YP_003024034.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
4.727 Conservation Score
PhyloP 470way
0.666 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.998 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Vus+ Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
10563T>A
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

10563 (T > G)

General info

Mitimpact ID
MI.15886
Chr
chrM
Start
10563
Ref
T
Alt
G
Gene symbol
MT-ND4L Extended gene annotation
Gene position
94
Gene start
10470
Gene end
10766
Gene strand
+
Codon substitution
TGC/GGC
AA pos
32
AA ref
C
AA alt
G
Functional effect
missense
OMIM ID
516004
HGVS
NC_012920.1:g.10563T>G
HGNC ID
7460
RC complex
I
Ensembl gene ID
ENSG00000212907
Ensembl protein ID
ENSP00000354728
Ensembl transcript ID
ENST00000361335
Uniprot ID
P03901
Uniprot name
NU4LM_HUMAN
Ncbi gene ID
4539
Ncbi protein ID
YP_003024034.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
4.727 Conservation Score
PhyloP 470way
0.666 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.998 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Ambiguous Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
High Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Vus+ Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
10563T>G
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 10563 (T/C) 10563 (T/A) 10563 (T/G)
~ 10563 (TGC/CGC) 10563 (TGC/AGC) 10563 (TGC/GGC)
MitImpact id MI.15884 MI.15885 MI.15886
Chr chrM chrM chrM
Start 10563 10563 10563
Ref T T T
Alt C A G
Gene symbol MT-ND4L MT-ND4L MT-ND4L
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4L mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4L mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4L
Gene position 94 94 94
Gene start 10470 10470 10470
Gene end 10766 10766 10766
Gene strand + + +
Codon substitution TGC/CGC TGC/AGC TGC/GGC
AA position 32 32 32
AA ref C C C
AA alt R S G
Functional effect general missense missense missense
Functional effect detailed missense missense missense
OMIM id 516004 516004 516004
HGVS NC_012920.1:g.10563T>C NC_012920.1:g.10563T>A NC_012920.1:g.10563T>G
HGNC id 7460 7460 7460
Respiratory Chain complex I I I
Ensembl gene id ENSG00000212907 ENSG00000212907 ENSG00000212907
Ensembl transcript id ENST00000361335 ENST00000361335 ENST00000361335
Ensembl protein id ENSP00000354728 ENSP00000354728 ENSP00000354728
Uniprot id P03901 P03901 P03901
Uniprot name NU4LM_HUMAN NU4LM_HUMAN NU4LM_HUMAN
Ncbi gene id 4539 4539 4539
Ncbi protein id YP_003024034.1 YP_003024034.1 YP_003024034.1
PhyloP 100V 4.727 4.727 4.727
PhyloP 470Way 0.666 0.666 0.666
PhastCons 100V 1 1 1
PhastCons 470Way 0.998 0.998 0.998
PolyPhen2 probably_damaging probably_damaging probably_damaging
PolyPhen2 score 1.0 1.0 1.0
SIFT neutral neutral neutral
SIFT score 0.14 0.3 0.19
SIFT4G Damaging Damaging Damaging
SIFT4G score 0.0 0.0 0.0
VEST Neutral Neutral Neutral
VEST pvalue 0.25 0.38 0.31
VEST FDR 0.45 0.5 0.5
Mitoclass.1 damaging neutral damaging
SNPDryad Pathogenic Pathogenic Pathogenic
SNPDryad score 1.0 0.97 1.0
MutationTaster Disease automatic Disease Disease
MutationTaster score 1 0.999534 0.999758
MutationTaster converted rankscore 0.81001 0.47451 0.48800
MutationTaster model simple_aae simple_aae simple_aae
MutationTaster AAE C32R C32S C32G
fathmm Tolerated Tolerated Tolerated
fathmm score 1.74 2.05 2.1
fathmm converted rankscore 0.26301 0.20664 0.19990
AlphaMissense likely_pathogenic likely_pathogenic ambiguous
AlphaMissense score 0.9568 0.74 0.5544
CADD Deleterious Deleterious Deleterious
CADD score 3.343631 3.372774 3.162797
CADD phred 22.9 22.9 22.6
PROVEAN Damaging Damaging Damaging
PROVEAN score -11.74 -9.77 -11.74
MutationAssessor . . high
MutationAssessor score . . 4.325
EFIN SP Neutral Neutral Neutral
EFIN SP score 0.654 0.69 0.64
EFIN HD Damaging Damaging Damaging
EFIN HD score 0.068 0.166 0.096
MLC Deleterious Deleterious Deleterious
MLC score 0.96752972 0.96752972 0.96752972
PANTHER score . . .
PhD-SNP score . . .
APOGEE1 Neutral Neutral Neutral
APOGEE1 score 0.42 0.32 0.36
APOGEE2 Likely-pathogenic VUS+ VUS+
APOGEE2 score 0.840262220797977 0.577413541068555 0.70824974695514
CAROL deleterious deleterious deleterious
CAROL score 1.0 1.0 1.0
Condel neutral neutral neutral
Condel score 0.07 0.15 0.1
COVEC WMV deleterious neutral deleterious
COVEC WMV score 2 -2 1
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.89 0.75 0.82
DEOGEN2 Tolerated Tolerated Tolerated
DEOGEN2 score 0.195885 0.114082 0.115699
DEOGEN2 converted rankscore 0.55210 0.43161 0.43448
Meta-SNP . . .
Meta-SNP score . . .
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -3.55 -3.55 -3.55
SIFT_transf medium impact medium impact medium impact
SIFT transf score -0.23 0.01 -0.14
MutationAssessor transf high impact medium impact medium impact
MutationAssessor transf score 2.18 -0.2 1.5
CHASM Neutral Neutral Neutral
CHASM pvalue 0.36 0.7 0.62
CHASM FDR 0.8 0.85 0.8
ClinVar id 9706.0 . .
ClinVar Allele id 24745.0 . .
ClinVar CLNDISDB MONDO:MONDO:0023113,MedGen:CN280943 . .
ClinVar CLNDN Familial_colorectal_cancer . .
ClinVar CLNSIG Pathogenic . .
MITOMAP Disease Clinical info . . .
MITOMAP Disease Status . . .
MITOMAP Disease Hom/Het ./. ./. ./.
MITOMAP General GenBank Freq . . .
MITOMAP General GenBank Seqs . . .
MITOMAP General Curated refs . . .
MITOMAP Variant Class . . .
gnomAD 3.1 AN 56433.0 . .
gnomAD 3.1 AC Homo 0.0 . .
gnomAD 3.1 AF Hom 0.0 . .
gnomAD 3.1 AC Het 0.0 . .
gnomAD 3.1 AF Het 0.0 . .
gnomAD 3.1 filter npg . .
HelixMTdb AC Hom . . .
HelixMTdb AF Hom . . .
HelixMTdb AC Het . . .
HelixMTdb AF Het . . .
HelixMTdb mean ARF . . .
HelixMTdb max ARF . . .
ToMMo 54KJPN AC . . .
ToMMo 54KJPN AF . . .
ToMMo 54KJPN AN . . .
COSMIC 90 . . .
dbSNP 156 id rs267606892 . .
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend