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NM_000414.4(HSD17B4):c.587C>T (p.Ala196Val) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 21, 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:
RCV002034370.4

Allele description [Variation Report for NM_000414.4(HSD17B4):c.587C>T (p.Ala196Val)]

NM_000414.4(HSD17B4):c.587C>T (p.Ala196Val)

Gene:
HSD17B4:hydroxysteroid 17-beta dehydrogenase 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q23.1
Genomic location:
Preferred name:
NM_000414.4(HSD17B4):c.587C>T (p.Ala196Val)
HGVS:
  • NC_000005.10:g.119478986C>T
  • NG_008182.1:g.31534C>T
  • NM_000414.4:c.587C>TMANE SELECT
  • NM_001199291.3:c.662C>T
  • NM_001199292.2:c.533C>T
  • NM_001292027.2:c.515C>T
  • NM_001292028.2:c.167C>T
  • NM_001374497.1:c.578C>T
  • NM_001374498.1:c.587C>T
  • NM_001374499.1:c.260C>T
  • NM_001374500.1:c.146C>T
  • NM_001374501.1:c.176C>T
  • NM_001374502.1:c.176C>T
  • NM_001374503.1:c.176C>T
  • NP_000405.1:p.Ala196Val
  • NP_001186220.1:p.Ala221Val
  • NP_001186221.1:p.Ala178Val
  • NP_001278956.1:p.Ala172Val
  • NP_001278957.1:p.Ala56Val
  • NP_001361426.1:p.Ala193Val
  • NP_001361427.1:p.Ala196Val
  • NP_001361428.1:p.Ala87Val
  • NP_001361429.1:p.Ala49Val
  • NP_001361430.1:p.Ala59Val
  • NP_001361431.1:p.Ala59Val
  • NP_001361432.1:p.Ala59Val
  • NC_000005.9:g.118814681C>T
  • NM_000414.3:c.587C>T
  • NR_164653.1:n.666C>T
  • NR_164654.1:n.854C>T
Protein change:
A172V
Links:
dbSNP: rs550705310
NCBI 1000 Genomes Browser:
rs550705310
Molecular consequence:
  • NM_000414.4:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199291.3:c.662C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199292.2:c.533C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001292027.2:c.515C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001292028.2:c.167C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374497.1:c.578C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374498.1:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374499.1:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374500.1:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374501.1:c.176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374502.1:c.176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374503.1:c.176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164653.1:n.666C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_164654.1:n.854C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Bifunctional peroxisomal enzyme deficiency (DBIF)
Synonyms:
D-bifunctional protein deficiency; DBP deficiency; D-bifunctional enzyme deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009855; MedGen: C0342870; OMIM: 261515
Name:
Perrault syndrome
Synonyms:
Gonadal dysgenesis with auditory dysfunction, autosomal recessive inheritance
Identifiers:
MONDO: MONDO:0017312; MedGen: C0685838; Orphanet: 2855; OMIM: PS233400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002307555Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 21, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency.

Lieber DS, Hershman SG, Slate NG, Calvo SE, Sims KB, Schmahmann JD, Mootha VK.

BMC Med Genet. 2014 Mar 6;15:30. doi: 10.1186/1471-2350-15-30.

PubMed [citation]
PMID:
24602372
PMCID:
PMC4015298

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002307555.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 196 of the HSD17B4 protein (p.Ala196Val). This variant is present in population databases (rs550705310, gnomAD 0.006%). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (PMID: 24602372). 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: 1522331). 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 HSD17B4 protein function with a positive predictive value of 95%. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024