ClinVar Miner

Submissions for variant NM_000286.3(PEX12):c.625C>T (p.Gln209Ter) (rs61752106)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671389 SCV000796361 likely pathogenic Infantile Refsum's disease; Peroxisome biogenesis disorder 3A 2017-12-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781711 SCV000919974 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2018-08-13 criteria provided, single submitter clinical testing Variant summary: PEX12 c.625C>T (p.Gln209X) 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 (e.g., p.Leu245fsX19). The variant allele was found at a frequency of 2.8e-05 in 246262 control chromosomes. c.625C>T has been reported in the literature in individuals affected with Zellweger Syndrome. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence showing a reduction in PEX12 mRNA in patient fibroblasts, as well as <10% of normal activity in dihydroxyacetonephosphate acyltransferase (DHAPAT) activity (Gootjes_2004). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000819199 SCV000959846 pathogenic Peroxisome biogenesis disorder 3A 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln209*) in the PEX12 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs61752106, ExAC 0.02%). This variant has been observed in combination with another PEX12 variant in an individual affected with Zellweger syndrome spectrum (PMID: 14571262). ClinVar contains an entry for this variant (Variation ID: 555548). Loss-of-function variants in PEX12 are known to be pathogenic (PMID: 9090384, 9632816, 21031596). For these reasons, this variant has been classified as Pathogenic.

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