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14596 (A > T)

General info

Mitimpact ID
MI.24026
Chr
chrM
Start
14596
Ref
A
Alt
T
Gene symbol
MT-ND6 Extended gene annotation
Gene position
78
Gene start
14149
Gene end
14673
Gene strand
-
Codon substitution
ATT/ATA
AA pos
26
AA ref
I
AA alt
M
Functional effect
missense
OMIM ID
516006
HGVS
NC_012920.1:g.14596A>T
HGNC ID
7462
RC complex
I
Ensembl gene ID
ENSG00000198695
Ensembl protein ID
ENSP00000354665
Ensembl transcript ID
ENST00000361681
Uniprot ID
P03923
Uniprot name
NU6M_HUMAN
Ncbi gene ID
4541
Ncbi protein ID
YP_003024037.1
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Conservation

PhyloP 100v
0.69 Conservation Score
PhyloP 470way
0.819 Conservation Score
PhastCons 100v
0.503 Conservation Score
PhastCons 470way
0.996 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
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
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
Medium Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
Neutral Score and details of the predictor
PhD-SNP
Disease Score and details of the predictor

Pathogenicity meta-predictors

APOGEE1
Pathogenic 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
.
Meta SNP
Disease Score and details of the meta-predictor

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
9690
Clinvar ALLELEID
24729
Clinvar CLNDISDB
Mondo:mondo:0010772, medgen:c1839040, omim:500001, orphanet:99718;

human phenotype ontology:hp:0001086, human phenotype ontology:hp:0001112, mondo:mondo:0010788, medgen:c0917796, omim:535000, orphanet:104
Clinvar CLNDN
Leber optic atrophy and dystonia;

leber optic atrophy
Clinvar CLNSIG
Pathogenic
MITOMAP Allele
14596A>T
MITOMAP Disease Clinical info
Lhon with hereditary spastic dystonia
MITOMAP Disease Status
Reported [vus]
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.0%
MITOMAP General GenBank Seqs
0
MITOMAP General GenBank Curated refs
8644732 15972314 29987491 20301353 17123466
MITOMAP Variant Class
disease
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
.

14596 (A > C)

General info

Mitimpact ID
MI.24027
Chr
chrM
Start
14596
Ref
A
Alt
C
Gene symbol
MT-ND6 Extended gene annotation
Gene position
78
Gene start
14149
Gene end
14673
Gene strand
-
Codon substitution
ATT/ATG
AA pos
26
AA ref
I
AA alt
M
Functional effect
missense
OMIM ID
516006
HGVS
NC_012920.1:g.14596A>C
HGNC ID
7462
RC complex
I
Ensembl gene ID
ENSG00000198695
Ensembl protein ID
ENSP00000354665
Ensembl transcript ID
ENST00000361681
Uniprot ID
P03923
Uniprot name
NU6M_HUMAN
Ncbi gene ID
4541
Ncbi protein ID
YP_003024037.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.69 Conservation Score
PhyloP 470way
0.819 Conservation Score
PhastCons 100v
0.503 Conservation Score
PhastCons 470way
0.996 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
Neutral Score and details of the predictor
MutationTaster
.
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
Medium Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
Neutral Score and details of the predictor
PhD-SNP
Disease Score and details of the predictor

Pathogenicity meta-predictors

APOGEE1
Pathogenic 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
Damaging Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor

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
14596A>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.0016%
MITOMAP General GenBank Seqs
1
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
polymorphism
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
.
~ 14596 (A/T) 14596 (A/C)
~ 14596 (ATT/ATA) 14596 (ATT/ATG)
MitImpact id MI.24026 MI.24027
Chr chrM chrM
Start 14596 14596
Ref A A
Alt T C
Gene symbol MT-ND6 MT-ND6
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 6 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 6
Gene position 78 78
Gene start 14149 14149
Gene end 14673 14673
Gene strand - -
Codon substitution ATT/ATA ATT/ATG
AA position 26 26
AA ref I I
AA alt M M
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516006 516006
HGVS NC_012920.1:g.14596A>T NC_012920.1:g.14596A>C
HGNC id 7462 7462
Respiratory Chain complex I I
Ensembl gene id ENSG00000198695 ENSG00000198695
Ensembl transcript id ENST00000361681 ENST00000361681
Ensembl protein id ENSP00000354665 ENSP00000354665
Uniprot id P03923 P03923
Uniprot name NU6M_HUMAN NU6M_HUMAN
Ncbi gene id 4541 4541
Ncbi protein id YP_003024037.1 YP_003024037.1
PhyloP 100V 0.69 0.69
PhyloP 470Way 0.819 0.819
PhastCons 100V 0.503 0.503
PhastCons 470Way 0.996 0.996
PolyPhen2 probably_damaging probably_damaging
PolyPhen2 score 1 1
SIFT neutral neutral
SIFT score 0.26 0.26
SIFT4G Damaging Damaging
SIFT4G score 0.004 0.004
VEST Neutral Neutral
VEST pvalue 0.55 0.55
VEST FDR 0.6 0.6
Mitoclass.1 damaging damaging
SNPDryad Neutral Neutral
SNPDryad score 0.87 0.87
MutationTaster . .
MutationTaster score . .
MutationTaster converted rankscore . .
MutationTaster model . .
MutationTaster AAE . .
fathmm . Tolerated
fathmm score . 2.1
fathmm converted rankscore . 0.19990
AlphaMissense ambiguous ambiguous
AlphaMissense score 0.3909 0.3909
CADD Deleterious Deleterious
CADD score 2.989791 2.878382
CADD phred 22.2 21.8
PROVEAN Damaging Damaging
PROVEAN score -2.79 -2.79
MutationAssessor medium medium
MutationAssessor score 2.43 2.43
EFIN SP Damaging Damaging
EFIN SP score 0.248 0.248
EFIN HD Damaging Damaging
EFIN HD score 0.2 0.2
MLC Deleterious Deleterious
MLC score 0.69406723 0.69406723
PANTHER score 0.472 0.472
PhD-SNP score 0.653 0.653
APOGEE1 Pathogenic Pathogenic
APOGEE1 score 0.95 0.94
APOGEE2 Likely-pathogenic Likely-pathogenic
APOGEE2 score 0.863323738802127 0.863323738802127
CAROL deleterious deleterious
CAROL score 1.0 1.0
Condel neutral neutral
Condel score 0.13 0.13
COVEC WMV deleterious deleterious
COVEC WMV score 1 1
MtoolBox deleterious deleterious
MtoolBox DS 0.75 0.75
DEOGEN2 . Damaging
DEOGEN2 score . 0.575089
DEOGEN2 converted rankscore . 0.85994
Meta-SNP Disease Disease
Meta-SNP score 0.704 0.704
PolyPhen2 transf low impact low impact
PolyPhen2 transf score -3.55 -3.55
SIFT_transf medium impact medium impact
SIFT transf score -0.05 -0.05
MutationAssessor transf medium impact medium impact
MutationAssessor transf score 1.46 1.46
CHASM Neutral Neutral
CHASM pvalue 0.81 0.81
CHASM FDR 0.85 0.85
ClinVar id 9690.0 .
ClinVar Allele id 24729.0 .
ClinVar CLNDISDB MONDO:MONDO:0010772,MedGen:C1839040,OMIM:500001,Orphanet:99718|Human_Phenotype_Ontology:HP:0001086,Human_Phenotype_Ontology:HP:0001112,MONDO:MONDO:0010788,MedGen:C0917796,OMIM:535000,Orphanet:104 .
ClinVar CLNDN Leber_optic_atrophy_and_dystonia|Leber_optic_atrophy .
ClinVar CLNSIG Pathogenic .
MITOMAP Disease Clinical info LHON with hereditary spastic dystonia .
MITOMAP Disease Status Reported [VUS] .
MITOMAP Disease Hom/Het +/- ./.
MITOMAP General GenBank Freq 0.0% 0.0016%
MITOMAP General GenBank Seqs 0 1
MITOMAP General Curated refs 8644732;15972314;29987491;20301353;17123466 .
MITOMAP Variant Class disease polymorphism
gnomAD 3.1 AN . .
gnomAD 3.1 AC Homo . .
gnomAD 3.1 AF Hom . .
gnomAD 3.1 AC Het . .
gnomAD 3.1 AF Het . .
gnomAD 3.1 filter . .
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 . .
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