ClinVar Miner

Submissions for variant NM_001017989.3(OPA3):c.143-24456G>C (rs80356523)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004461 SCV000485243 pathogenic 3-Methylglutaconic aciduria type 3 2016-02-29 criteria provided, single submitter clinical testing
GeneReviews RCV000004461 SCV000041510 pathologic 3-Methylglutaconic aciduria type 3 2009-03-31 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000798887 SCV000938526 pathogenic 3-Methylglutaconic aciduria type 3; Optic atrophy and cataract, autosomal dominant 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.
OMIM RCV000004461 SCV000024634 pathogenic 3-Methylglutaconic aciduria type 3 2001-12-01 no assertion criteria provided literature only

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