Submissions for variant NM_000286.3(PEX12):c.334C>T (p.Gln112Ter)

dbSNP: rs776731688

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000675037	SCV000800467	likely pathogenic	Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger)	2018-06-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000679868	SCV000807239	pathogenic	Peroxisome biogenesis disorder 3A (Zellweger)	2024-02-14	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000679868	SCV000996241	pathogenic	Peroxisome biogenesis disorder 3A (Zellweger)	2019-01-31	criteria provided, single submitter	clinical testing	This nonsense variant found in exon 2 of 3 encodes for a premature stop codon and is predicted to result in loss of normal protein function. This variant has been previously reported as a homozygous change in association with intellectual disability and inborn error of metabolism (PMID: 27124789). It is absent from the gnomAD population database and is present in the heterozygous state in the ExAC population database at a frequency of 0.001% (1/120740) and thus is presumed to be rare. This variant has been classified in ClinVar as a pathogenic and likely pathogenic variant (Variation ID: 191074). In silico analyses support a deleterious effect of the c.334C>T (p.Gln112Ter) variant on protein function. Based on the available evidence, the c.334C>T (p.Gln112Ter) variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000679868	SCV001592170	pathogenic	Peroxisome biogenesis disorder 3A (Zellweger)	2024-10-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln112*) in the PEX12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX12 are known to be pathogenic (PMID: 9090384, 9632816, 21031596). This variant is present in population databases (rs776731688, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PEX12-related conditions. ClinVar contains an entry for this variant (Variation ID: 191074). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004552945	SCV004107277	likely pathogenic	PEX12-related disorder	2023-07-14	criteria provided, single submitter	clinical testing	The PEX12 c.334C>T variant is predicted to result in premature protein termination (p.Gln112*). This variant was reported in fetus with neurological and other congenital anomalies (Yang et al 2014. PubMed ID: 25326635). To our knowledge, it has not been reported in individuals with peroxisomal storage disorder. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-33904403-G-A). Nonsense variants in PEX12 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000679868	SCV004804681	likely pathogenic	Peroxisome biogenesis disorder 3A (Zellweger)	2024-03-17	criteria provided, single submitter	research
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000171254	SCV000221451	likely pathogenic	not provided		flagged submission	research