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8519 (G > A)

General info

Mitimpact ID
MI.1769
Chr
chrM
Start
8519
Ref
G
Alt
A
Gene symbol
MT-ATP8 Extended gene annotation
Gene position
154
Gene start
8366
Gene end
8572
Gene strand
+
Codon substitution
GAA/AAA
AA pos
52
AA ref
E
AA alt
K
Functional effect
missense
OMIM ID
516070
HGVS
NC_012920.1:g.8519G>A
HGNC ID
7415
RC complex
V
Ensembl gene ID
ENSG00000228253
Ensembl protein ID
ENSP00000355265
Ensembl transcript ID
ENST00000361851
Uniprot ID
P03928
Uniprot name
ATP8_HUMAN
Ncbi gene ID
4509
Ncbi protein ID
YP_003024030.1
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Conservation

PhyloP 100v
-0.027 Conservation Score
PhyloP 470way
0.965 Conservation Score
PhastCons 100v
0.002 Conservation Score
PhastCons 470way
0.291 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging 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
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely benign 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
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic 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
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
235671
Clinvar ALLELEID
237351
Clinvar CLNDISDB
Medgen:cn517202;

mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Not provided;

leigh syndrome
Clinvar CLNSIG
Benign/likely benign
MITOMAP Allele
8519G>A
MITOMAP Disease Clinical info
Possible susceptibility to bullous pemphigoid
MITOMAP Disease Status
Reported
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.2601%
MITOMAP General GenBank Seqs
159
MITOMAP General GenBank Curated refs
15338331 31824475 25941154
MITOMAP Variant Class
polymorphism;disease
Gnomad AN
56419
Gnomad AC hom
144
Gnomad AF hom
0.0025523
Gnomad AC het
7
Gnomad AF het
0.000124
Gnomad filter
Pass
HelixMTdb AC hom
811
HelixMTdb AF hom
0.0041381
HelixMTdb AC het
11
HelixMTdb AF het
5.61e-05
HelixMTdb mean ARF
0.3183
HelixMTdb max ARF
0.8285
ToMMo JPN54K AC
2
ToMMo JPN54K AF
3.7e-05
ToMMo JPN54K AN
54302
COSMIC 90
.
dbSNP 156
rs878853091

Residue interaction

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

Compensated Pathogenic Deviations

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

8519 (G > C)

General info

Mitimpact ID
MI.1770
Chr
chrM
Start
8519
Ref
G
Alt
C
Gene symbol
MT-ATP8 Extended gene annotation
Gene position
154
Gene start
8366
Gene end
8572
Gene strand
+
Codon substitution
GAA/CAA
AA pos
52
AA ref
E
AA alt
Q
Functional effect
missense
OMIM ID
516070
HGVS
NC_012920.1:g.8519G>C
HGNC ID
7415
RC complex
V
Ensembl gene ID
ENSG00000228253
Ensembl protein ID
ENSP00000355265
Ensembl transcript ID
ENST00000361851
Uniprot ID
P03928
Uniprot name
ATP8_HUMAN
Ncbi gene ID
4509
Ncbi protein ID
YP_003024030.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-0.027 Conservation Score
PhyloP 470way
0.965 Conservation Score
PhastCons 100v
0.002 Conservation Score
PhastCons 470way
0.291 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging 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
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
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
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Likely-benign 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
8519G>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.0033%
MITOMAP General GenBank Seqs
2
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
polymorphism
Gnomad AN
56434
Gnomad AC hom
1
Gnomad AF hom
1.77e-05
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Pass
HelixMTdb AC hom
11
HelixMTdb AF hom
5.61e-05
HelixMTdb AC het
1
HelixMTdb AF het
5.1e-06
HelixMTdb mean ARF
0.16568
HelixMTdb max ARF
0.16568
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
.
~ 8519 (G/A) 8519 (G/C)
~ 8519 (GAA/AAA) 8519 (GAA/CAA)
MitImpact id MI.1769 MI.1770
Chr chrM chrM
Start 8519 8519
Ref G G
Alt A C
Gene symbol MT-ATP8 MT-ATP8
Extended annotation mitochondrially encoded ATP synthase membrane subunit 8 mitochondrially encoded ATP synthase membrane subunit 8
Gene position 154 154
Gene start 8366 8366
Gene end 8572 8572
Gene strand + +
Codon substitution GAA/AAA GAA/CAA
AA position 52 52
AA ref E E
AA alt K Q
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516070 516070
HGVS NC_012920.1:g.8519G>A NC_012920.1:g.8519G>C
HGNC id 7415 7415
Respiratory Chain complex V V
Ensembl gene id ENSG00000228253 ENSG00000228253
Ensembl transcript id ENST00000361851 ENST00000361851
Ensembl protein id ENSP00000355265 ENSP00000355265
Uniprot id P03928 P03928
Uniprot name ATP8_HUMAN ATP8_HUMAN
Ncbi gene id 4509 4509
Ncbi protein id YP_003024030.1 YP_003024030.1
PhyloP 100V -0.027 -0.027
PhyloP 470Way 0.965 0.965
PhastCons 100V 0.002 0.002
PhastCons 470Way 0.291 0.291
PolyPhen2 probably_damaging probably_damaging
PolyPhen2 score 0.97 0.98
SIFT neutral neutral
SIFT score 0.92 0.57
SIFT4G Tolerated Tolerated
SIFT4G score 0.068 0.133
VEST Neutral Neutral
VEST pvalue 0.61315205 0.62290357
VEST FDR 0.85 0.85
Mitoclass.1 neutral neutral
SNPDryad Neutral Neutral
SNPDryad score 0.71 0.11
MutationTaster Disease Disease
MutationTaster score 0.936221 0.76695
MutationTaster converted rankscore 0.37148 0.34105
MutationTaster model simple_aae simple_aae
MutationTaster AAE E52K E52Q
fathmm Tolerated Tolerated
fathmm score 1.84 1.81
fathmm converted rankscore 0.24656 0.25182
AlphaMissense likely_benign likely_benign
AlphaMissense score 0.1544 0.1197
CADD Deleterious Neutral
CADD score 4.51607 1.76764
CADD phred 24.3 14.8
PROVEAN Damaging Tolerated
PROVEAN score -3.08 -1.93
MutationAssessor . .
MutationAssessor score . .
EFIN SP Neutral Neutral
EFIN SP score 0.996 0.994
EFIN HD Neutral Neutral
EFIN HD score 0.676 0.702
MLC Neutral Neutral
MLC score 0.03874706 0.03874706
PANTHER score . .
PhD-SNP score . .
APOGEE1 Pathogenic Pathogenic
APOGEE1 score 0.53 0.61
APOGEE2 Likely-benign Likely-benign
APOGEE2 score 0.158153357532382 0.157289784655979
CAROL neutral deleterious
CAROL score 0.97 0.98
Condel deleterious neutral
Condel score 0.48 0.3
COVEC WMV deleterious deleterious
COVEC WMV score 1 1
MtoolBox deleterious deleterious
MtoolBox DS 0.8 0.71
DEOGEN2 Tolerated Tolerated
DEOGEN2 score 0.117339 0.05527
DEOGEN2 converted rankscore 0.43735 0.29960
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf low impact low impact
PolyPhen2 transf score -2.19 -2.36
SIFT_transf medium impact medium impact
SIFT transf score 0.89 0.36
MutationAssessor transf medium impact medium impact
MutationAssessor transf score 0.78 0.69
CHASM Neutral Neutral
CHASM pvalue 0.75 0.75
CHASM FDR 0.85 0.85
ClinVar id 235671.0 .
ClinVar Allele id 237351.0 .
ClinVar CLNDISDB MedGen:CN517202|MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 .
ClinVar CLNDN not_provided|Leigh_syndrome .
ClinVar CLNSIG Benign/Likely_benign .
MITOMAP Disease Clinical info Possible susceptibility to bullous pemphigoid .
MITOMAP Disease Status Reported .
MITOMAP Disease Hom/Het +/- ./.
MITOMAP General GenBank Freq 0.2601% 0.0033%
MITOMAP General GenBank Seqs 159 2
MITOMAP General Curated refs 15338331;31824475;25941154 .
MITOMAP Variant Class polymorphism;disease polymorphism
gnomAD 3.1 AN 56419.0 56434.0
gnomAD 3.1 AC Homo 144.0 1.0
gnomAD 3.1 AF Hom 0.00255233 1.77198e-05
gnomAD 3.1 AC Het 7.0 0.0
gnomAD 3.1 AF Het 0.000124072 0.0
gnomAD 3.1 filter PASS PASS
HelixMTdb AC Hom 811.0 11.0
HelixMTdb AF Hom 0.004138114 5.6127315e-05
HelixMTdb AC Het 11.0 1.0
HelixMTdb AF Het 5.6127315e-05 5.1024836e-06
HelixMTdb mean ARF 0.3183 0.16568
HelixMTdb max ARF 0.8285 0.16568
ToMMo 54KJPN AC 2 .
ToMMo 54KJPN AF 3.7e-05 .
ToMMo 54KJPN AN 54302 .
COSMIC 90 . .
dbSNP 156 id rs878853091 .
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