ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.1273G>A (p.Val425Met)

gnomAD frequency: 0.00001  dbSNP: rs121907988
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001262594 SCV001440523 pathogenic Neu-Laxova syndrome 1 2019-01-01 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous.
Invitae RCV000004072 SCV002172431 uncertain significance PHGDH deficiency 2022-03-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 425 of the PHGDH protein (p.Val425Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with phosphoglycerate dehydrogenase deficiency (PMID: 11055895, 22393170, 29018476, 32404165). ClinVar contains an entry for this variant (Variation ID: 3868). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects PHGDH function (PMID: 11055895, 19235232). 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.
OMIM RCV000004072 SCV000024238 pathogenic PHGDH deficiency 2000-12-01 no assertion criteria provided literature only

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