Submissions for variant NM_004493.3(HSD17B10):c.439C>T (p.Arg147Cys)

dbSNP: rs1064794694

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484484	SCV000569745	pathogenic	not provided	2022-08-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12555940, 15342248, 34765396)
Ambry Genetics	RCV000623879	SCV000741370	likely pathogenic	Inborn genetic diseases	2016-04-26	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001755724	SCV001994793	likely pathogenic	HSD10 mitochondrial disease	2021-10-18	criteria provided, single submitter	clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV002274038	SCV002558977	pathogenic	Neurodevelopmental delay		criteria provided, single submitter	clinical testing
Breda Genetics srl	RCV001755724	SCV002588729	likely pathogenic	HSD10 mitochondrial disease	2021-07-20	criteria provided, single submitter	clinical testing	The variant c.439C>T (p.Arg147Cys) in the HSD17B10 gene, rs1064794694, reference transcript NM_001037811.2 is reported as likely pathogenic for a congenital disease in ClinVar (Variation ID: 420778) and in Global Variome shared LOVD 3.0 (genomic variant: #0000576627). There is no information on frequency in gnomAD. The nucleotide position is highly conserved across 35 mammalian species (GERP RS:5.81). In silico analysis indicates that the variant might be damaging.
CeGaT Center for Human Genetics Tuebingen	RCV000484484	SCV004032944	likely pathogenic	not provided	2023-08-01	criteria provided, single submitter	clinical testing	HSD17B10: PM2, PM6, PS4:Moderate, PP2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000484484	SCV005727711	uncertain significance	not provided	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 147 of the HSD17B10 protein (p.Arg147Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of HSD17B10-related conditions (PMID: 34765396). ClinVar contains an entry for this variant (Variation ID: 420778). 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 HSD17B10 protein function. 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.
GenomeConnect, ClinGen	RCV001755724	SCV002074966	not provided	HSD10 mitochondrial disease		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 10-28-2020 by Lab or GTR ID UCLA Molecular Diagnostics Laboratory. 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.