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NM_000414.4(HSD17B4):c.101C>T (p.Ala34Val) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 22, 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:
RCV003764860.1

Allele description [Variation Report for NM_000414.4(HSD17B4):c.101C>T (p.Ala34Val)]

NM_000414.4(HSD17B4):c.101C>T (p.Ala34Val)

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.101C>T (p.Ala34Val)
HGVS:
  • NC_000005.10:g.119456357C>T
  • NG_008182.1:g.8905C>T
  • NM_000414.4:c.101C>TMANE SELECT
  • NM_001199291.3:c.111C>T
  • NM_001199292.2:c.58+3724C>T
  • NM_001292027.2:c.-37C>T
  • NM_001292028.2:c.-311C>T
  • NP_000405.1:p.Ala34Val
  • NP_001186220.1:p.Ser37=
  • NC_000005.9:g.118792052C>T
  • NM_000414.3:c.101C>T
Protein change:
A34V; ALA34VAL
Links:
OMIM: 601860.0010; dbSNP: rs587777442
NCBI 1000 Genomes Browser:
rs587777442
Molecular consequence:
  • NM_001292027.2:c.-37C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001292028.2:c.-311C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001199292.2:c.58+3724C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000414.4:c.101C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199291.3:c.111C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004569794Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 22, 2024)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.

Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T.

Am J Hum Genet. 2006 Jan;78(1):112-24. Epub 2005 Nov 15.

PubMed [citation]
PMID:
16385454
PMCID:
PMC1380208

Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency.

McMillan HJ, Worthylake T, Schwartzentruber J, Gottlieb CC, Lawrence SE, Mackenzie A, Beaulieu CL, Mooyer PA; FORGE Canada Consortium., Wanders RJ, Majewski J, Bulman DE, Geraghty MT, Ferdinandusse S, Boycott KM.

Orphanet J Rare Dis. 2012 Nov 22;7:90. doi: 10.1186/1750-1172-7-90.

PubMed [citation]
PMID:
23181892
PMCID:
PMC3551712
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004569794.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 34 of the HSD17B4 protein (p.Ala34Val). This variant is present in population databases (rs587777442, gnomAD 0.006%). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (PMID: 16385454, 23181892, 34719423). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 137616). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HSD17B4 protein function. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jul 7, 2024