ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.3208-1G>A (rs1057517518)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000599082 SCV000707639 pathogenic not provided 2017-04-06 criteria provided, single submitter clinical testing
GeneDx RCV000599082 SCV000710583 likely pathogenic not provided 2018-02-15 criteria provided, single submitter clinical testing The c.3208-1G>A variant in the PEX1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 20. 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.3208-1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3208-1G>A as a likely pathogenic variant.
Invitae RCV000411432 SCV001227260 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2020-01-20 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 of the PEX1 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 not been reported in the literature in individuals with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371765). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl RCV000411432 SCV000487694 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2019-07-12 no assertion criteria provided clinical testing
Counsyl RCV000409017 SCV000487695 likely pathogenic Peroxisome biogenesis disorder 1B 2019-07-12 no assertion criteria provided clinical testing

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