chr3-193664952-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_130837.3(OPA1):c.2734C>T(p.Arg912Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_130837.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA1 | NM_130837.3 | c.2734C>T | p.Arg912Ter | stop_gained | 27/31 | ENST00000361510.8 | |
LOC102724808 | XR_924835.3 | n.420+3968G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA1 | ENST00000361510.8 | c.2734C>T | p.Arg912Ter | stop_gained | 27/31 | 5 | NM_130837.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456126Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2AN XY: 724720
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | This sequence change creates a premature translational stop signal (p.Arg857*) in the OPA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 104 amino acid(s) of the OPA1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with dominant optic atrophy (PMID: 28926202, 34242285). ClinVar contains an entry for this variant (Variation ID: 195896). This variant disrupts a region of the OPA1 protein in which other variant(s) (p.Val903Glyfs*3) have been determined to be pathogenic (PMID: 11017079, 26385429). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2020 | Observed in the heterozygous state in individuals with optic atrophy in the published literature (Rocca et al., 2015; Santarelli et al., 2015); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 19319978, 28926202, 25794858, 25564500) - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 12, 2021 | This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at