Submissions for variant NM_000191.3(HMGCL):c.425C>T (p.Ser142Phe)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702964	SCV005203901	likely pathogenic	Deficiency of hydroxymethylglutaryl-CoA lyase	2024-07-01	criteria provided, single submitter	clinical testing	Variant summary: HMGCL c.425C>T (p.Ser142Phe) results in a non-conservative amino acid change located in the Pyruvate carboxyltransferase domain (IPR000891) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251476 control chromosomes. c.425C>T has been reported in the literature in a compound heterozygous individual affected with HMG-CoA Lyase Deficiency (Menao_2009). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <5% of normal activity in an in vitro assay (Menao_2009). The following publication have been ascertained in the context of this evaluation (PMID: 19177531). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.