rs747468360
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001689.5(ATP5MC3):c.265G>T(p.Gly89Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Consequence
ATP5MC3
NM_001689.5 missense
NM_001689.5 missense
Scores
11
6
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.91
Genes affected
ATP5MC3 (HGNC:843): (ATP synthase membrane subunit c locus 3) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene is one of three genes that encode subunit c of the proton channel. Each of the three genes have distinct mitochondrial import sequences but encode the identical mature protein. Alternatively spliced transcript variants encoding different proteins have been identified. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ATP5MC3 | NM_001689.5 | c.265G>T | p.Gly89Cys | missense_variant | Exon 4 of 5 | ENST00000284727.9 | NP_001680.1 | |
| ATP5MC3 | NM_001002258.5 | c.265G>T | p.Gly89Cys | missense_variant | Exon 3 of 4 | NP_001002258.1 | ||
| ATP5MC3 | NM_001190329.2 | c.265G>T | p.Gly89Cys | missense_variant | Exon 4 of 4 | NP_001177258.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ATP5MC3 | ENST00000284727.9 | c.265G>T | p.Gly89Cys | missense_variant | Exon 4 of 5 | 1 | NM_001689.5 | ENSP00000284727.4 | ||
| ATP5MC3 | ENST00000392541.3 | c.265G>T | p.Gly89Cys | missense_variant | Exon 3 of 4 | 1 | ENSP00000376324.3 | |||
| ATP5MC3 | ENST00000409194.5 | c.265G>T | p.Gly89Cys | missense_variant | Exon 4 of 5 | 2 | ENSP00000387317.1 | |||
| ATP5MC3 | ENST00000497075.5 | n.393G>T | non_coding_transcript_exon_variant | Exon 4 of 4 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ExAC
AF:
AC:
2
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of disorder (P = 0.027);Loss of disorder (P = 0.027);Loss of disorder (P = 0.027);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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