ClinVar Miner

Submissions for variant NM_153818.1(PEX10):c.600+1G>A (rs267608183)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666073 SCV000790311 pathogenic Peroxisome biogenesis disorder 6A; Peroxisome biogenesis disorder 6B 2017-03-10 criteria provided, single submitter clinical testing
GeneDx RCV000519441 SCV000617242 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing The c.600+1G>A variant in the PEX10 gene has been reported previously in association withautosomal recessive Zellweger syndrome when present in the homozygous state or when in trans withanother disease-causing variant (Warren et al., 1998; Steinberg et al., 2009). One functional studyindicated the c.600+1G>A variant produces truncated PEX10 mRNAS and results in lack of significantmatrix-protein import (Warren et al., 1998). This splice site variant destroys the canonical splicedonor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormalmessage that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if themessage is used for protein translation. The c.600+1G>A variant is not observed at a significantfrequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015;Exome Variant Server). We interpret c.600+1G>A as a pathogenic variant.
Invitae RCV000817369 SCV000957924 pathogenic Peroxisome biogenesis disorder, complementation group 7 2018-11-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the PEX10 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs267608183, ExAC 0.006%). This variant has been observed in an individual affected with Zellweger syndrome (PMID: 9683594). ClinVar contains an entry for this variant (Variation ID: 6770). Experimental studies have shown that this splice change results in exon skipping and absent protein activity (PMID: 9683594). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX10 are known to be pathogenic (PMID: 9683594, 10862081, 21031596). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007172 SCV000027368 pathogenic Peroxisome biogenesis disorder 6A 1998-08-01 no assertion criteria provided literature only

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