Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669254 | SCV000793988 | pathogenic | Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger) | 2017-09-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001008292 | SCV001168060 | likely pathogenic | not provided | 2019-10-21 | criteria provided, single submitter | clinical testing | Observed with a variant on the opposite allele (in trans) in a patient with Zellweger syndrome in the published literature (Chang et al., 1997; Chang and Gould, 1998; Ebberink et al., 2011); Frameshift variant predicted to result in protein truncation, as the last 111 amino acids are replaced with 13 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9090384, 9792857, 21031596) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174916 | SCV001338351 | pathogenic | Peroxisome biogenesis disorder | 2022-06-06 | criteria provided, single submitter | clinical testing | Variant summary: PEX12 c.744dupT (p.Thr249TyrfsX14) 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 8e-06 in 250122 control chromosomes (gnomAD). c.744dupT has been reported in the literature in individuals affected with Zellweger Syndrome (e.g. Chang_1997, Ebberink_2011). One of these patients was shown to have impaired PTS1- and PTS2-protein transport, and reduced PEX12 mRNA levels (Chang_1998). These data indicate that the variant is likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001333351 | SCV001592168 | pathogenic | Peroxisome biogenesis disorder 3A (Zellweger) | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr249Tyrfs*14) in the PEX12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 111 amino acid(s) of the PEX12 protein. This variant is present in population databases (rs61752108, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 9090384, 9792857). This variant is also known as c.744_745insT. ClinVar contains an entry for this variant (Variation ID: 553741). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects PEX12 function (PMID: 9090384). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the PEX12 protein in which other variant(s) (p.Leu297Thrfs*12) have been determined to be pathogenic (PMID: 9792857, 14571262, 21031596, 25287621, 26094004). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001333351 | SCV004201431 | pathogenic | Peroxisome biogenesis disorder 3A (Zellweger) | 2023-09-25 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV001333351 | SCV000028420 | pathogenic | Peroxisome biogenesis disorder 3A (Zellweger) | 1997-04-01 | no assertion criteria provided | literature only |