Submissions for variant NM_006623.4(PHGDH):c.40A>G (p.Ser14Gly)

dbSNP: rs1448633854

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520350	SCV000621644	uncertain significance	not provided	2017-10-24	criteria provided, single submitter	clinical testing	The S14G variant in the PHGDH gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The S14G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S14G as a variant of uncertain significance.
Invitae	RCV001275504	SCV003508280	uncertain significance	PHGDH deficiency	2021-09-24	criteria provided, single submitter	clinical testing	This sequence change replaces serine with glycine at codon 14 of the PHGDH protein (p.Ser14Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PHGDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 452805). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV003338640	SCV004049031	uncertain significance	Neu-Laxova syndrome 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001275504	SCV004049032	uncertain significance	PHGDH deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275504	SCV001460684	uncertain significance	PHGDH deficiency	2020-09-16	no assertion criteria provided	clinical testing