Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV001818138 | SCV002069634 | likely pathogenic | not provided | 2020-09-28 | criteria provided, single submitter | clinical testing | |
Clinical Biochemistry Laboratory, |
RCV000005156 | SCV004190281 | likely pathogenic | Testosterone 17-beta-dehydrogenase deficiency | 2023-11-20 | criteria provided, single submitter | clinical testing | ACMG:PM1 PM2 PP2 PP3 |
Invitae | RCV001818138 | SCV004296026 | pathogenic | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 130 of the HSD17B3 protein (p.Asn130Ser). This variant is present in population databases (rs119481079, gnomAD 0.007%). This missense change has been observed in individual(s) with 17β-HSD3 deficiency (PMID: 25740850, 27307783, 36154887). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 4880). 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) performed at Invitae indicates that this missense variant is expected to disrupt HSD17B3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects HSD17B3 function (PMID: 9709959). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000005156 | SCV000025333 | pathogenic | Testosterone 17-beta-dehydrogenase deficiency | 1998-08-01 | no assertion criteria provided | literature only |