NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 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:: RCV000688945.11

Allele description [Variation Report for NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser)]

NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser)

Genes:

LOC129994460:ATAC-STARR-seq lymphoblastoid active region 22989 [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.46G>A (p.Gly16Ser)

HGVS:

NC_000005.10:g.119452621G>A
NG_008182.1:g.5169G>A
NM_000414.4:c.46G>AMANE SELECT
NM_001199291.3:c.-133G>A
NM_001199292.2:c.46G>A
NM_001292027.2:c.-92G>A
NM_001292028.2:c.-554G>A
NP_000405.1:p.Gly16Ser
NP_001186221.1:p.Gly16Ser
NC_000005.9:g.118788316G>A
NM_000414.3:c.46G>A
P51659:p.Gly16Ser

Protein change:

G16S; GLY16SER

Links:

UniProtKB: P51659#VAR_037576; OMIM: 601860.0003; dbSNP: rs137853096

NCBI 1000 Genomes Browser:

rs137853096

Molecular consequence:

NM_001199291.3:c.-133G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001292027.2:c.-92G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001292028.2:c.-554G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000414.4:c.46G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199292.2:c.46G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000816576	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16385454, 25967389, 9482850, 10419023, 10497229, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000816576

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

PubMed (6)
[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

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

Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia.

Konkoľová J, Petrovič R, Chandoga J, Repiský M, Zelinková H, Kršiaková J, Kolníková M, Kantarská D, Šutovský S, Böhmer D.

Gene. 2015 Aug 15;568(1):61-8. doi: 10.1016/j.gene.2015.05.020. Epub 2015 May 9.

PubMed [citation]

PMID:: 25967389

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000816576.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 16 of the HSD17B4 protein (p.Gly16Ser). This variant is present in population databases (rs137853096, gnomAD 0.04%). This missense change has been observed in individuals with D-bifunctional protein deficiency (PMID: 9482850, 16385454, 25967389). ClinVar contains an entry for this variant (Variation ID: 7655). 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%. Experimental studies have shown that this missense change affects HSD17B4 function (PMID: 9482850, 10419023, 10497229). For these reasons, this variant has been classified as 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: Oct 8, 2024

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Relating variation to medicine