ClinVar Miner

Submissions for variant NM_001172435.2(RAB3GAP1):c.748+1G>A (rs587776651)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578621 SCV000680759 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing The c.748+1G>A variant in the RAB3GAP1 gene has been reported previously in association with Warburg Micro syndrome, and is considered a founder mutation in the Turkish population (Handley et al., 2013). This splice site variant destroys the canonical splice donor site of intron 8. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.748+1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.748+1G>A as a pathogenic variant.
Invitae RCV000578621 SCV000932155 pathogenic not provided 2018-08-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 of the RAB3GAP1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been  reported as homozygous in several individuals and families affected with Warburg Micro syndrome (PMID: 15696165, 26852512, 23420520). ClinVar contains an entry for this variant (Variation ID: 7058). Studies of RNA derived from the cells of affected individuals have shown that this splice change results in skipping of exon 8, and a subsequent frameshift (PMID: 15696165). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007474 SCV000027674 pathogenic Warburg micro syndrome 1 2013-05-01 no assertion criteria provided literature only
GeneReviews RCV000007474 SCV000778354 pathogenic Warburg micro syndrome 1 2017-10-31 no assertion criteria provided literature only

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