Submissions for variant NM_006623.4(PHGDH):c.296C>G (p.Pro99Arg)

gnomAD frequency: 0.00032  dbSNP: rs182600362

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000880956	SCV001024089	likely benign	PHGDH deficiency	2025-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000880956	SCV001255495	likely benign	PHGDH deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome-Nilou Lab	RCV003338837	SCV004049051	likely benign	Neu-Laxova syndrome 1	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000880956	SCV004049052	likely benign	PHGDH deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV004997462	SCV005621662	benign	not specified	2024-10-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004997462	SCV005727215	likely benign	not specified	2024-11-04	criteria provided, single submitter	clinical testing	Variant summary: PHGDH c.296C>G (p.Pro99Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 251486 control chromosomes, predominantly at a frequency of 0.0084 within the Latino subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in PHGDH causing Phosphoglycerate Dehydrogenase Deficiency phenotype (0.0026). To our knowledge, no occurrence of c.296C>G in individuals affected with Phosphoglycerate Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 709534). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc.	RCV000880956	SCV001463180	uncertain significance	PHGDH deficiency	2020-02-13	no assertion criteria provided	clinical testing