rs371938193
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_007103.4(NDUFV1):c.770G>A(p.Arg257His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
NDUFV1
NM_007103.4 missense
NM_007103.4 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 9.65
Genes affected
NDUFV1 (HGNC:7716): (NADH:ubiquinone oxidoreductase core subunit V1) The mitochondrial respiratory chain provides energy to cells via oxidative phosphorylation and consists of four membrane-bound electron-transporting protein complexes (I-IV) and an ATP synthase (complex V). This gene encodes a 51 kDa subunit of the NADH:ubiquinone oxidoreductase complex I; a large complex with at least 45 nuclear and mitochondrial encoded subunits that liberates electrons from NADH and channels them to ubiquinone. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-biding sites. Defects in complex I are a common cause of mitochondrial dysfunction; a syndrome that occurs in approximately 1 in 10,000 live births. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity NDUV1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
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AC:
2
AN:
152228
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Cov.:
32
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GnomAD2 exomes AF: 0.0000199 AC: 5AN: 251488 AF XY: 0.0000368 show subpopulations
GnomAD2 exomes
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5
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251488
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727246 show subpopulations
GnomAD4 exome
AF:
AC:
8
AN:
1461890
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
727246
Gnomad4 AFR exome
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0
AN:
33480
Gnomad4 AMR exome
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AC:
1
AN:
44724
Gnomad4 ASJ exome
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0
AN:
26136
Gnomad4 EAS exome
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0
AN:
39700
Gnomad4 SAS exome
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2
AN:
86258
Gnomad4 FIN exome
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AC:
0
AN:
53420
Gnomad4 NFE exome
AF:
AC:
5
AN:
1112008
Gnomad4 Remaining exome
AF:
AC:
0
AN:
60396
Heterozygous variant carriers
0
1
2
4
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6
0.00
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0.80
0.95
Allele balance
Exome Het
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Age
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152228
Hom.:
Cov.:
32
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AC XY:
2
AN XY:
74368
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0
Gnomad4 NFE
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AC:
0.0000293927
AN:
0.0000293927
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0
AN:
0
Heterozygous variant carriers
0
0
1
1
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2
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Genome Het
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Bravo
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ESP6500AA
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0
ESP6500EA
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1
ExAC
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AC:
3
EpiCase
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EpiControl
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Jan 23, 2017
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;.;.
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
.;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;D;D
Sift4G
Benign
.;T;T;T;T
Polyphen
D;D;B;P;P
Vest4
0.79, 0.80, 0.77, 0.79
MVP
0.93
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Mutation Taster
=5/95
disease causing
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at