ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.517del (p.Ser173fs)

gnomAD frequency: 0.00001  dbSNP: rs61753212
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673874 SCV000799126 pathogenic Peroxisome biogenesis disorder 4A (Zellweger); Peroxisome biogenesis disorder 4B 2018-04-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193475 SCV001362343 pathogenic Peroxisome biogenesis disorder 2021-06-11 criteria provided, single submitter clinical testing Variant summary: PEX6 c.517delA (p.Ser173AlafsX33) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1e-05 in 197224 control chromosomes (gnomAD). c.517delA has been reported in the literature in at least two unrelated, compound heterozygous individuals affected with Zellweger Syndrome (Steinberg 2004, Ebberink 2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001193475 SCV002236006 pathogenic Peroxisome biogenesis disorder 2023-02-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser173Alafs*33) in the PEX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX6 are known to be pathogenic (PMID: 8670792, 19877282, 21031596). This variant is present in population databases (rs61753212, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of PEX6-related conditions (PMID: 15542397). ClinVar contains an entry for this variant (Variation ID: 557701). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001830460 SCV002077341 pathogenic Zellweger spectrum disorders 2020-06-19 no assertion criteria provided clinical testing

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