NM_000197.2(HSD17B3):c.673G>A (p.Val225Met) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV003553946.2

Allele description [Variation Report for NM_000197.2(HSD17B3):c.673G>A (p.Val225Met)]

NM_000197.2(HSD17B3):c.673G>A (p.Val225Met)

Gene:

HSD17B3:hydroxysteroid 17-beta dehydrogenase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Preferred name:

NM_000197.2(HSD17B3):c.673G>A (p.Val225Met)

HGVS:

NC_000009.12:g.96240907C>T
NG_008157.1:g.66246G>A
NM_000197.2:c.673G>AMANE SELECT
NP_000188.1:p.Val225Met
LRG_1296t1:c.673G>A
LRG_1296:g.66246G>A
LRG_1296p1:p.Val225Met
NC_000009.11:g.99003189C>T
NM_000197.1:c.673G>A
NR_182427.1:n.3440G>A

Protein change:

V225M

Molecular consequence:

NM_000197.2:c.673G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_182427.1:n.3440G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004296023	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25740850, 28617986, 34009138, 32372306, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296023

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 11, 2024)

germline

clinical testing

PubMed (5)
[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

Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development.

Phelan N, Williams EL, Cardamone S, Lee M, Creighton SM, Rumsby G, Conway GS.

Eur J Endocrinol. 2015 Jun;172(6):745-51. doi: 10.1530/EJE-14-0994. Epub 2015 Mar 4.

PubMed [citation]

PMID:: 25740850

A novel HSD17B3 gene mutation in a 46,XY female-phenotype newborn identified by whole-exome sequencing.

Bertalan R, Admoni O, Bashamboo A, Tenenbaum-Rakover Y, McElreavey K.

Clin Endocrinol (Oxf). 2017 Oct;87(4):407-408. doi: 10.1111/cen.13396. Epub 2017 Jul 24. No abstract available.

PubMed [citation]

PMID:: 28617986

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296023.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 225 of the HSD17B3 protein (p.Val225Met). This variant is present in population databases (rs768355659, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive 17-beta hydroxysteroid dehydrogenase 3 deficiency and/or clinical features of HDS17B3-related conditions (PMID: 25740850, 28617986, 32372306, 34009138). It has also been observed to segregate with disease in related individuals. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change is associated with inconclusive levels of altered splicing (PMID: 32372306). 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.

#	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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