ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.1359A>C (p.Glu453Asp)

gnomAD frequency: 0.00004  dbSNP: rs202164519
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000505504 SCV000599696 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2013-11-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002056895 SCV002419292 benign not provided 2023-01-20 criteria provided, single submitter clinical testing
Mendelics RCV000505504 SCV002518814 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV003243160 SCV003943968 uncertain significance Inborn genetic diseases 2023-05-17 criteria provided, single submitter clinical testing The c.1359A>C (p.E453D) alteration is located in exon 12 (coding exon 12) of the PHEX gene. This alteration results from a A to C substitution at nucleotide position 1359, causing the glutamic acid (E) at amino acid position 453 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003403182 SCV004122450 uncertain significance not specified 2023-10-04 criteria provided, single submitter clinical testing Variant summary: PHEX c.1359A>C (p.Glu453Asp) results in a conservative amino acid change located in the Peptidase M13, N-terminal domain (IPR018497) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 183326 control chromosomes including 3 hemizygotes suggesting a benign role. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1359A>C in individuals affected with X-Linked Hypophosphatemic Rickets and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, one submitter classified the variant as benign, and a third submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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