ClinVar Miner

Submissions for variant NM_000198.4(HSD3B2):c.558dup (p.Thr187fs)

dbSNP: rs770815049
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001659693 SCV001880910 pathogenic not provided 2020-10-20 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.
Labcorp Genetics (formerly Invitae), Labcorp RCV001659693 SCV002247016 pathogenic not provided 2023-03-08 criteria provided, single submitter clinical testing This variant is also known as 186/insC/187. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminal region of the HSD3B2 protein, which has been demonstrated to be critical for enzymatic activity (PMID: 18252794). While functional studies have not been performed to directly test the effect of this variant on HSD3B2 protein function, this suggests that disruption of this region of the protein is causative of disease. ClinVar contains an entry for this variant (Variation ID: 12185). This premature translational stop signal has been observed in individual(s) with 3-beta-hydroxysteroid dehydrogenase deficiency (PMID: 1363812). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770815049, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Thr187Hisfs*17) in the HSD3B2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 186 amino acid(s) of the HSD3B2 protein.
OMIM RCV000012968 SCV000033213 pathogenic 3 beta-Hydroxysteroid dehydrogenase deficiency 1992-07-01 no assertion criteria provided literature only
Natera, Inc. RCV000012968 SCV002094668 pathogenic 3 beta-Hydroxysteroid dehydrogenase deficiency 2020-11-16 no assertion criteria provided clinical testing

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