ClinVar Miner

Submissions for variant NM_025136.4(OPA3):c.143-1G>C (rs80356523)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798887 SCV000938526 pathogenic 3-Methylglutaconic aciduria type 3; Optic atrophy 3 2018-11-26 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in the last intron (intron 1) of the OPA3 gene. While this 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 (ExAC no frequency). This variant has been observed in combination with another OPA3 variant in individuals affected with 3-methylglutaconic aciduria (PMID: 11668429, 25201222, 26190011). ClinVar contains an entry for this variant (Variation ID: 4239). Nucleotide substitutions within 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. Transcriptional studies using fibroblasts from homozygous individuals indicate that this variant leads to aberrant splicing and mRNA loss (PMID: 11668429). For these reasons, this variant has been classified as Pathogenic.
Myriad Women's Health, 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 Praxis fuer Humangenetik Tuebingen RCV001093243 SCV001250129 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
OMIM RCV000004461 SCV000024634 pathogenic 3-Methylglutaconic aciduria type 3 2001-12-01 no assertion criteria provided literature only
GeneReviews RCV000004461 SCV000041510 pathologic 3-Methylglutaconic aciduria type 3 2009-03-31 no assertion criteria provided curation Converted during submission to Pathogenic.

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