ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.1117G>A (p.Ala373Thr)

dbSNP: rs201553627
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000785912 SCV000924488 uncertain significance PHGDH deficiency 2018-06-15 criteria provided, single submitter research The homozygous p.Ala373Thr variant was identified by our study in one individual with phosphoglycerate dehydrogenase deficiency. This variant has been identified in the literature in one affected homozygous proband of Turkish ancestry with consanguineous parents (Tabatabaie et al. 2009, PMID:19235232). This variant has been identified in <0.01% (1/33582) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201553627). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The Alanine (Ala) at position 373 is highly conserved in mammals and evolutionarily distant species, raising the possibility that a change at this position may not be tolerated. Computational prediction tools do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000785912 SCV003523411 uncertain significance PHGDH deficiency 2022-07-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 373 of the PHGDH protein (p.Ala373Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with phosphoglycerate dehydrogenase deficiency (PMID: 19235232). ClinVar contains an entry for this variant (Variation ID: 635039). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects PHGDH function (PMID: 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.
Genome-Nilou Lab RCV003338792 SCV004049115 uncertain significance Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000785912 SCV004049116 uncertain significance PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing

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