NM_000198.4(HSD3B2):c.931C>T (p.Gln311Ter) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001206762.6

Allele description [Variation Report for NM_000198.4(HSD3B2):c.931C>T (p.Gln311Ter)]

NM_000198.4(HSD3B2):c.931C>T (p.Gln311Ter)

Gene:

HSD3B2:hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p12

Genomic location:

Preferred name:

NM_000198.4(HSD3B2):c.931C>T (p.Gln311Ter)

HGVS:

NC_000001.11:g.119422432C>T
NG_013349.1:g.12502C>T
NM_000198.4:c.931C>TMANE SELECT
NM_001166120.2:c.931C>T
NP_000189.1:p.Gln311Ter
NP_001159592.1:p.Gln311Ter
NC_000001.10:g.119965055C>T
NM_000198.3:c.931C>T

Protein change:

Q311*

Links:

dbSNP: rs781213951

NCBI 1000 Genomes Browser:

rs781213951

Molecular consequence:

NM_000198.4:c.931C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001166120.2:c.931C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001378086	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27899157, 28207417, 1825279, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001378086

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 17, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, Lambeth L, Bouty A, Knarston IM, Tan TY, Cameron F, Werther G, Hutson J, O'Connell M, Grover SR, Heloury Y, Zacharin M, Bergman P, Kimber C, Brown J, Webb N, Hunter MF, et al.

Genome Biol. 2016 Nov 29;17(1):243.

PubMed [citation]

PMID:: 27899157
PMCID:: PMC5126855

Adrenarche unmasks compound heterozygous 3β-hydroxysteroid dehydrogenase deficiency: c.244G>A (p.Ala82Thr) and the novel 931C>T (p.Gln311*) variant in a non-salt wasting, severely undervirilised 46XY.

Teasdale SL, Morton A.

J Pediatr Endocrinol Metab. 2017 Mar 1;30(3):355-360. doi: 10.1515/jpem-2016-0348.

PubMed [citation]

PMID:: 28207417

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001378086.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This premature translational stop signal has been observed in individual(s) with congenital adrenal hyperplasia or an unspecified disorder of sexual development (PMID: 27899157, 28207417). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the C-terminus of the HSD3B2 protein, which has been demonstrated to be critical for enzymatic activity (PMID: 1825279). 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: 937691). This variant is present in population databases (rs781213951, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln311*) in the HSD3B2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 62 amino acid(s) of the HSD3B2 protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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