19-45529145-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001017989.3(OPA3):āc.454C>Gā(p.Leu152Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,457,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
OPA3
NM_001017989.3 missense
NM_001017989.3 missense
Scores
2
7
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.46
Genes affected
OPA3 (HGNC:8142): (outer mitochondrial membrane lipid metabolism regulator OPA3) The mouse ortholog of this protein co-purifies with the mitochondrial inner membrane. Mutations in this gene have been shown to result in 3-methylglutaconic aciduria type III and autosomal dominant optic atrophy and cataract. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
In a chain Optic atrophy 3 protein (size 177) in uniprot entity OPA3_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_001017989.3
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41224355).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000422 AC: 1AN: 236892Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130248
GnomAD3 exomes
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1
AN:
236892
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130248
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1457198Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 724876
GnomAD4 exome
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AC:
4
AN:
1457198
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Cov.:
31
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1
AN XY:
724876
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
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1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.2168);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at