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3946 (G > A)

General info

Mitimpact ID
MI.12086
Chr
chrM
Start
3946
Ref
G
Alt
A
Gene symbol
MT-ND1 Extended gene annotation
Gene position
640
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
GAA/AAA
AA pos
214
AA ref
E
AA alt
K
Functional effect
missense
OMIM ID
516000
HGVS
NC_012920.1:g.3946G>A
HGNC ID
7455
RC complex
I
Ensembl gene ID
ENSG00000198888
Ensembl protein ID
ENSP00000354687
Ensembl transcript ID
ENST00000361390
Uniprot ID
P03886
Uniprot name
NU1M_HUMAN
Ncbi gene ID
4535
Ncbi protein ID
YP_003024026.1
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Conservation

PhyloP 100v
9.438 Conservation Score
PhyloP 470way
0.42 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.005 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
Pathogenic 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
High 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
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
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
9734
Clinvar ALLELEID
24773
Clinvar CLNDISDB
Mondo:mondo:0010789, medgen:c0162671, omim:540000, orphanet:550;

human phenotype ontology:hp:0001086, human phenotype ontology:hp:0001112, mondo:mondo:0010788, medgen:c0917796, omim:535000, orphanet:104;

mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Juvenile myopathy, encephalopathy, lactic acidosis and stroke;

leber optic atrophy;

leigh syndrome
Clinvar CLNSIG
Pathogenic/likely pathogenic
MITOMAP Allele
3946G>A
MITOMAP Disease Clinical info
Melas
MITOMAP Disease Status
Cfrm [lp]
MITOMAP Disease Hom/Het
+/+
MITOMAP General GenBank Freq
0.0016%
MITOMAP General GenBank Seqs
1
MITOMAP General GenBank Curated refs
31996177 38465286 16849371 31665838 18402672 26741492 28429146 15972314 15466014 21364701 21457906 29253894
MITOMAP Variant Class
polymorphism;disease
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
1
HelixMTdb AF het
5.1e-06
HelixMTdb mean ARF
0.10345
HelixMTdb max ARF
0.10345
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
COSM1138367
dbSNP 156
rs199476123

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
.

3946 (G > C)

General info

Mitimpact ID
MI.12085
Chr
chrM
Start
3946
Ref
G
Alt
C
Gene symbol
MT-ND1 Extended gene annotation
Gene position
640
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
GAA/CAA
AA pos
214
AA ref
E
AA alt
Q
Functional effect
missense
OMIM ID
516000
HGVS
NC_012920.1:g.3946G>C
HGNC ID
7455
RC complex
I
Ensembl gene ID
ENSG00000198888
Ensembl protein ID
ENSP00000354687
Ensembl transcript ID
ENST00000361390
Uniprot ID
P03886
Uniprot name
NU1M_HUMAN
Ncbi gene ID
4535
Ncbi protein ID
YP_003024026.1
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Powered by MitoWheel

Conservation

PhyloP 100v
9.438 Conservation Score
PhyloP 470way
0.42 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.005 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
Pathogenic Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Polymorphism 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
High 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
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
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
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
3946G>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
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
.
~ 3946 (G/A) 3946 (G/C)
~ 3946 (GAA/AAA) 3946 (GAA/CAA)
MitImpact id MI.12086 MI.12085
Chr chrM chrM
Start 3946 3946
Ref G G
Alt A C
Gene symbol MT-ND1 MT-ND1
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1
Gene position 640 640
Gene start 3307 3307
Gene end 4262 4262
Gene strand + +
Codon substitution GAA/AAA GAA/CAA
AA position 214 214
AA ref E E
AA alt K Q
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516000 516000
HGVS NC_012920.1:g.3946G>A NC_012920.1:g.3946G>C
HGNC id 7455 7455
Respiratory Chain complex I I
Ensembl gene id ENSG00000198888 ENSG00000198888
Ensembl transcript id ENST00000361390 ENST00000361390
Ensembl protein id ENSP00000354687 ENSP00000354687
Uniprot id P03886 P03886
Uniprot name NU1M_HUMAN NU1M_HUMAN
Ncbi gene id 4535 4535
Ncbi protein id YP_003024026.1 YP_003024026.1
PhyloP 100V 9.438 9.438
PhyloP 470Way 0.42 0.42
PhastCons 100V 1 1
PhastCons 470Way 0.005 0.005
PolyPhen2 probably_damaging probably_damaging
PolyPhen2 score 1.0 1.0
SIFT neutral neutral
SIFT score 0.29 0.29
SIFT4G Damaging Damaging
SIFT4G score 0.005 0.001
VEST Pathogenic Pathogenic
VEST pvalue 0.02 0.05
VEST FDR 0.35 0.35
Mitoclass.1 damaging damaging
SNPDryad Pathogenic Pathogenic
SNPDryad score 0.99 0.91
MutationTaster Disease automatic Polymorphism
MutationTaster score 6.73736e-05 0.999928
MutationTaster converted rankscore 0.19363 0.19486
MutationTaster model complex_aae complex_aae
MutationTaster AAE E214K E214Q
fathmm Tolerated Tolerated
fathmm score 2.16 2.14
fathmm converted rankscore 0.19166 0.19450
AlphaMissense likely_pathogenic likely_pathogenic
AlphaMissense score 0.9434 0.869
CADD Deleterious Deleterious
CADD score 4.626318 3.446227
CADD phred 24.5 23.0
PROVEAN Damaging Damaging
PROVEAN score -3.79 -2.84
MutationAssessor high high
MutationAssessor score 4.625 4.97
EFIN SP Neutral Neutral
EFIN SP score 0.622 0.67
EFIN HD Neutral Neutral
EFIN HD score 0.386 0.496
MLC Deleterious Deleterious
MLC score 0.76769871 0.76769871
PANTHER score . .
PhD-SNP score . .
APOGEE1 Pathogenic Pathogenic
APOGEE1 score 0.66 0.62
APOGEE2 Likely-pathogenic Likely-pathogenic
APOGEE2 score 0.856520546574319 0.832158338089047
CAROL deleterious deleterious
CAROL score 1.0 1.0
Condel neutral neutral
Condel score 0.15 0.15
COVEC WMV deleterious deleterious
COVEC WMV score 2 2
MtoolBox deleterious deleterious
MtoolBox DS 0.91 0.87
DEOGEN2 Tolerated Tolerated
DEOGEN2 score 0.464324 0.470434
DEOGEN2 converted rankscore 0.79992 0.80356
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf low impact low impact
PolyPhen2 transf score -3.57 -3.57
SIFT_transf medium impact medium impact
SIFT transf score 0.06 0.06
MutationAssessor transf high impact high impact
MutationAssessor transf score 2.52 2.71
CHASM Neutral Neutral
CHASM pvalue 0.68 0.54
CHASM FDR 0.85 0.8
ClinVar id 9734.0 .
ClinVar Allele id 24773.0 .
ClinVar CLNDISDB MONDO:MONDO:0010789,MedGen:C0162671,OMIM:540000,Orphanet:550|Human_Phenotype_Ontology:HP:0001086,Human_Phenotype_Ontology:HP:0001112,MONDO:MONDO:0010788,MedGen:C0917796,OMIM:535000,Orphanet:104|MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 .
ClinVar CLNDN Juvenile_myopathy,_encephalopathy,_lactic_acidosis_AND_stroke|Leber_optic_atrophy|Leigh_syndrome .
ClinVar CLNSIG Pathogenic/Likely_pathogenic .
MITOMAP Disease Clinical info MELAS .
MITOMAP Disease Status Cfrm [LP] .
MITOMAP Disease Hom/Het +/+ ./.
MITOMAP General GenBank Freq 0.0016% .
MITOMAP General GenBank Seqs 1 .
MITOMAP General Curated refs 31996177;38465286;16849371;31665838;18402672;26741492;28429146;15972314;15466014;21364701;21457906;29253894 .
MITOMAP Variant Class polymorphism;disease .
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 0.0 .
HelixMTdb AF Hom 0.0 .
HelixMTdb AC Het 1.0 .
HelixMTdb AF Het 5.1024836e-06 .
HelixMTdb mean ARF 0.10345 .
HelixMTdb max ARF 0.10345 .
ToMMo 54KJPN AC . .
ToMMo 54KJPN AF . .
ToMMo 54KJPN AN . .
COSMIC 90 COSM1138367 .
dbSNP 156 id rs199476123 .
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