rs145999595
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_130837.3(OPA1):āc.2592T>Cā(p.Leu864=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00019 ( 0 hom., cov: 32)
Exomes š: 0.00036 ( 0 hom. )
Consequence
OPA1
NM_130837.3 synonymous
NM_130837.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.862
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 3-193662893-T-C is Benign according to our data. Variant chr3-193662893-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 382460.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=-0.862 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA1 | NM_130837.3 | c.2592T>C | p.Leu864= | synonymous_variant | 26/31 | ENST00000361510.8 | |
LOC102724808 | XR_924835.3 | n.420+6027A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA1 | ENST00000361510.8 | c.2592T>C | p.Leu864= | synonymous_variant | 26/31 | 5 | NM_130837.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000956 AC: 24AN: 251098Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135702
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GnomAD4 exome AF: 0.000359 AC: 525AN: 1461354Hom.: 0 Cov.: 31 AF XY: 0.000308 AC XY: 224AN XY: 726982
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GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74326
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 15, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | OPA1: BP4, BP7 - |
Autosomal dominant optic atrophy classic form Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
OPA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 06, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at