Submissions for variant NM_004493.3(HSD17B10):c.286G>A (p.Val96Met)

gnomAD frequency: 0.00001  dbSNP: rs965610533

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498369	SCV000590678	likely benign	not specified	2017-10-02	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002527159	SCV003350042	uncertain significance	not provided	2022-06-19	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 96 of the HSD17B10 protein (p.Val96Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HSD17B10-related conditions. ClinVar contains an entry for this variant (Variation ID: 432904). 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"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000498369	SCV005423140	uncertain significance	not specified	2024-10-16	criteria provided, single submitter	clinical testing	Variant summary: HSD17B10 c.286G>A (p.Val96Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 183114 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.286G>A in individuals affected with 2-Methyl-3-Hydroxybutyric Aciduria and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 432904). Based on the evidence outlined above, the variant was classified as uncertain significance.
GenomeConnect, ClinGen	RCV000509416	SCV000607246	not provided	HSD17B10-related disorder		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.