Submissions for variant NM_000444.6(PHEX):c.397C>T (p.Gln133Ter)

dbSNP: rs151306376

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497462	SCV000589348	pathogenic	not provided	2017-06-14	criteria provided, single submitter	clinical testing	The Q133X nonsense variant in the PHEX gene has been reported previously in association with X-linked hypophosphatemic rickets (Ruppe et al., 2011). Q133X is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000497462	SCV001205022	pathogenic	not provided	2024-03-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln133*) in the PHEX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hypophophatemic rickets (PMID: 21050253, 30682568). ClinVar contains an entry for this variant (Variation ID: 431828). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196900	SCV001367534	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2019-12-19	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM1,PM2,PP5.