ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.743C>A (p.Ala248Asp)

dbSNP: rs201782441
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644868 SCV000766583 uncertain significance PHGDH deficiency 2022-09-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 248 of the PHGDH protein (p.Ala248Asp). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PHGDH protein function. ClinVar contains an entry for this variant (Variation ID: 536420). This variant has not been reported in the literature in individuals affected with PHGDH-related conditions.
Ambry Genetics RCV002533268 SCV003633813 uncertain significance Inborn genetic diseases 2022-09-02 criteria provided, single submitter clinical testing The c.743C>A (p.A248D) alteration is located in exon 7 (coding exon 7) of the PHGDH gene. This alteration results from a C to A substitution at nucleotide position 743, causing the alanine (A) at amino acid position 248 to be replaced by an aspartic acid (D). Based on data from gnomAD, the A allele has an overall frequency of <0.001% (1/250070) total alleles studied. This alteration was found to be homozygous in a fetus with clinical features of Neu-Laxova syndrome (current proband / Ambry Internal Data). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003338712 SCV004049086 uncertain significance Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000644868 SCV004049087 uncertain significance PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing

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