ClinVar Miner

Submissions for variant NM_004813.4(PEX16):c.680G>A (p.Arg227Gln)

gnomAD frequency: 0.00001  dbSNP: rs754024503
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001004854 SCV001164330 uncertain significance Peroxisome biogenesis disorder 8A (Zellweger) 2018-12-03 criteria provided, single submitter research The homozygous p.Arg227Gln variant in PEX16 was identified by our study in two siblings with Peroxisome Biogenesis Disorder. A similar amino acid change has been reported in ClinVar as likely pathogenic previously (p.Arg227Trp), raising support for pathogenicity (ClinVar ID: 420154; PMID: 24091540). This variant has been identified in <0.01% (1/20846) of European (Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs754024503). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Arg227Gln variant is uncertain.
PreventionGenetics, part of Exact Sciences RCV003392731 SCV004119316 uncertain significance PEX16-related disorder 2024-04-03 no assertion criteria provided clinical testing The PEX16 c.680G>A variant is predicted to result in the amino acid substitution p.Arg227Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0048% of alleles in individuals of European (Finnish) descent in gnomAD. A different substitution at this amino acid position (p.Arg227Trp) has been reported in the compound heterozygous state along with a truncating variant as well as the homozygous state in patients with PEX16 related disorders (Ohba. 2013. PubMed ID: 24091540; Cheung. 2022. PubMed ID: 35106698). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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