Logo MitImpact
Home Description Output legend Molecular Dynamics How to cite License

4612 (T > C)

General info

Mitimpact ID
MI.13054
Chr
chrM
Start
4612
Ref
T
Alt
C
Gene symbol
MT-ND2 Extended gene annotation
Gene position
143
Gene start
4470
Gene end
5511
Gene strand
+
Codon substitution
ATA/ACA
AA pos
48
AA ref
M
AA alt
T
Functional effect
missense
OMIM ID
516001
HGVS
NC_012920.1:g.4612T>C
HGNC ID
7456
RC complex
I
Ensembl gene ID
ENSG00000198763
Ensembl protein ID
ENSP00000355046
Ensembl transcript ID
ENST00000361453
Uniprot ID
P03891
Uniprot name
NU2M_HUMAN
Ncbi gene ID
4536
Ncbi protein ID
YP_003024027.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.003 Conservation Score
PhyloP 470way
-0.456 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.01 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral 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
Benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Medium impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Low 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
692467
Clinvar ALLELEID
681003
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Leigh syndrome
Clinvar CLNSIG
Likely benign
MITOMAP Allele
4612T>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.0344%
MITOMAP General GenBank Seqs
21
MITOMAP General GenBank Curated refs
21185889 16714301
MITOMAP Variant Class
polymorphism
Gnomad AN
56433
Gnomad AC hom
12
Gnomad AF hom
0.0002126
Gnomad AC het
1
Gnomad AF het
1.77e-05
Gnomad filter
Pass
HelixMTdb AC hom
57
HelixMTdb AF hom
0.0002908
HelixMTdb AC het
6
HelixMTdb AF het
3.06e-05
HelixMTdb mean ARF
0.46641
HelixMTdb max ARF
0.88235
ToMMo JPN54K AC
241
ToMMo JPN54K AF
0.004438
ToMMo JPN54K AN
54302
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
.

4612 (T > A)

General info

Mitimpact ID
MI.13053
Chr
chrM
Start
4612
Ref
T
Alt
A
Gene symbol
MT-ND2 Extended gene annotation
Gene position
143
Gene start
4470
Gene end
5511
Gene strand
+
Codon substitution
ATA/AAA
AA pos
48
AA ref
M
AA alt
K
Functional effect
missense
OMIM ID
516001
HGVS
NC_012920.1:g.4612T>A
HGNC ID
7456
RC complex
I
Ensembl gene ID
ENSG00000198763
Ensembl protein ID
ENSP00000355046
Ensembl transcript ID
ENST00000361453
Uniprot ID
P03891
Uniprot name
NU2M_HUMAN
Ncbi gene ID
4536
Ncbi protein ID
YP_003024027.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.003 Conservation Score
PhyloP 470way
-0.456 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.01 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral 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-benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Medium impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Low 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
4612T>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
56432
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
.

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
.
~ 4612 (T/C) 4612 (T/A)
~ 4612 (ATA/ACA) 4612 (ATA/AAA)
MitImpact id MI.13054 MI.13053
Chr chrM chrM
Start 4612 4612
Ref T T
Alt C A
Gene symbol MT-ND2 MT-ND2
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2
Gene position 143 143
Gene start 4470 4470
Gene end 5511 5511
Gene strand + +
Codon substitution ATA/ACA ATA/AAA
AA position 48 48
AA ref M M
AA alt T K
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516001 516001
HGVS NC_012920.1:g.4612T>C NC_012920.1:g.4612T>A
HGNC id 7456 7456
Respiratory Chain complex I I
Ensembl gene id ENSG00000198763 ENSG00000198763
Ensembl transcript id ENST00000361453 ENST00000361453
Ensembl protein id ENSP00000355046 ENSP00000355046
Uniprot id P03891 P03891
Uniprot name NU2M_HUMAN NU2M_HUMAN
Ncbi gene id 4536 4536
Ncbi protein id YP_003024027.1 YP_003024027.1
PhyloP 100V 0.003 0.003
PhyloP 470Way -0.456 -0.456
PhastCons 100V 0 0
PhastCons 470Way 0.01 0.01
PolyPhen2 benign benign
PolyPhen2 score 0.0 0.12
SIFT neutral neutral
SIFT score 0.45 0.55
SIFT4G Tolerated Tolerated
SIFT4G score 0.217 0.166
VEST Neutral Neutral
VEST pvalue 0.22 0.16
VEST FDR 0.45 0.45
Mitoclass.1 neutral neutral
SNPDryad Neutral Neutral
SNPDryad score 0.01 0.33
MutationTaster . .
MutationTaster score . .
MutationTaster converted rankscore . .
MutationTaster model . .
MutationTaster AAE . .
fathmm . .
fathmm score . .
fathmm converted rankscore . .
AlphaMissense likely_benign likely_benign
AlphaMissense score 0.123 0.1932
CADD Neutral Neutral
CADD score -0.488579 0.664679
CADD phred 0.234 8.594
PROVEAN Tolerated Tolerated
PROVEAN score -0.01 -0.41
MutationAssessor neutral neutral
MutationAssessor score -1.01 -2.41
EFIN SP Neutral Neutral
EFIN SP score 0.97 0.912
EFIN HD Neutral Neutral
EFIN HD score 0.92 0.872
MLC Deleterious Deleterious
MLC score 0.57124751 0.57124751
PANTHER score . .
PhD-SNP score . .
APOGEE1 Neutral Neutral
APOGEE1 score 0.33 0.28
APOGEE2 Benign Likely-benign
APOGEE2 score 0.0244711848990281 0.090467068614132
CAROL neutral neutral
CAROL score 0.55 0.36
Condel deleterious deleterious
Condel score 0.73 0.72
COVEC WMV neutral neutral
COVEC WMV score -6 -6
MtoolBox neutral neutral
MtoolBox DS 0.21 0.33
DEOGEN2 . .
DEOGEN2 score . .
DEOGEN2 converted rankscore . .
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf medium impact medium impact
PolyPhen2 transf score 1.95 -0.01
SIFT_transf medium impact medium impact
SIFT transf score 0.16 0.26
MutationAssessor transf low impact low impact
MutationAssessor transf score -1.33 -2.52
CHASM Neutral Neutral
CHASM pvalue 0.11 0.17
CHASM FDR 0.8 0.8
ClinVar id 692467.0 .
ClinVar Allele id 681003.0 .
ClinVar CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 .
ClinVar CLNDN Leigh_syndrome .
ClinVar CLNSIG Likely_benign .
MITOMAP Disease Clinical info . .
MITOMAP Disease Status . .
MITOMAP Disease Hom/Het ./. ./.
MITOMAP General GenBank Freq 0.0344% .
MITOMAP General GenBank Seqs 21 .
MITOMAP General Curated refs 21185889;16714301 .
MITOMAP Variant Class polymorphism .
gnomAD 3.1 AN 56433.0 56432.0
gnomAD 3.1 AC Homo 12.0 0.0
gnomAD 3.1 AF Hom 0.000212642 0.0
gnomAD 3.1 AC Het 1.0 0.0
gnomAD 3.1 AF Het 1.77201e-05 0.0
gnomAD 3.1 filter PASS npg
HelixMTdb AC Hom 57.0 .
HelixMTdb AF Hom 0.00029084156 .
HelixMTdb AC Het 6.0 .
HelixMTdb AF Het 3.06149e-05 .
HelixMTdb mean ARF 0.46641 .
HelixMTdb max ARF 0.88235 .
ToMMo 54KJPN AC 241 .
ToMMo 54KJPN AF 0.004438 .
ToMMo 54KJPN AN 54302 .
COSMIC 90 . .
dbSNP 156 id . .
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