3-193615742-G-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_130837.3(OPA1):c.420G>T(p.Val140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00892 in 1,610,888 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0062 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0092 ( 88 hom. )
Consequence
OPA1
NM_130837.3 synonymous
NM_130837.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.654
Genes affected
OPA1 (HGNC:8140): (OPA1 mitochondrial dynamin like GTPase) The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 3-193615742-G-T is Benign according to our data. Variant chr3-193615742-G-T is described in ClinVar as [Benign]. Clinvar id is 95725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193615742-G-T is described in Lovd as [Benign]. Variant chr3-193615742-G-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.654 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00618 (941/152268) while in subpopulation SAS AF= 0.0104 (50/4816). AF 95% confidence interval is 0.00859. There are 7 homozygotes in gnomad4. There are 451 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OPA1 | NM_130837.3 | c.420G>T | p.Val140= | synonymous_variant | 3/31 | ENST00000361510.8 | NP_570850.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OPA1 | ENST00000361510.8 | c.420G>T | p.Val140= | synonymous_variant | 3/31 | 5 | NM_130837.3 | ENSP00000355324 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00618 AC: 940AN: 152150Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00836 AC: 2103AN: 251424Hom.: 19 AF XY: 0.00915 AC XY: 1243AN XY: 135882
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GnomAD4 exome AF: 0.00921 AC: 13436AN: 1458620Hom.: 88 Cov.: 29 AF XY: 0.00948 AC XY: 6881AN XY: 725850
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GnomAD4 genome AF: 0.00618 AC: 941AN: 152268Hom.: 7 Cov.: 33 AF XY: 0.00606 AC XY: 451AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:7
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | OPA1: BP4, BP7, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 23, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 29, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 01, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Autosomal dominant optic atrophy classic form Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at