ClinVar Miner

Submissions for variant NM_025136.4(OPA3):c.143-1G>C

dbSNP: rs80356523
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798887 SCV000938526 pathogenic 3-Methylglutaconic aciduria type 3; Optic atrophy 3 2023-12-06 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the OPA3 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with 3-methylglutaconic aciduria (PMID: 11668429, 25201222, 26190011). ClinVar contains an entry for this variant (Variation ID: 4239). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV000004461 SCV001193878 pathogenic 3-Methylglutaconic aciduria type 3 2019-12-20 criteria provided, single submitter clinical testing NM_025136.3(OPA3):c.143-1G>C is classified as pathogenic in the context of Costeff optic atrophy syndrome. Sources cited for classification include the following: PMID 15902555, 25201222, 11668429 and 20350831. Classification of NM_025136.3(OPA3):c.143-1G>C is based on the following criteria: The variant is located at a canonical splice site, is expected to disrupt gene function and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen RCV001093243 SCV001250129 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000798887 SCV002789638 pathogenic 3-Methylglutaconic aciduria type 3; Optic atrophy 3 2022-01-13 criteria provided, single submitter clinical testing
Baylor Genetics RCV000004461 SCV004209053 pathogenic 3-Methylglutaconic aciduria type 3 2023-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004461 SCV005203819 pathogenic 3-Methylglutaconic aciduria type 3 2024-07-02 criteria provided, single submitter clinical testing Variant summary: OPA3 c.143-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Anikster_2001). The variant was absent in 242140 control chromosomes. c.143-1G>C has been reported in the literature in multiple individuals affected with 3-Methylglutaconic Aciduria Type 3 (example, Anikster_2001). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 11668429). ClinVar contains an entry for this variant (Variation ID: 4239). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000004461 SCV000024634 pathogenic 3-Methylglutaconic aciduria type 3 2001-12-01 no assertion criteria provided literature only
GeneReviews RCV000004461 SCV000041510 not provided 3-Methylglutaconic aciduria type 3 no assertion provided literature only Accounts for 100% of pathogenic variants of individuals of Iraqi Jewish origin with Costeff syndrome
Natera, Inc. RCV000004461 SCV001454621 pathogenic 3-Methylglutaconic aciduria type 3 2020-09-16 no assertion criteria provided clinical testing

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