NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser) AND HSD17B4-Related Disorders

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 16, 2018
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:: RCV000779455.7

Allele description

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:: HSD17B4-Related Disorders
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000916080	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Oct 16, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16385454, 25967389, 26970254, 9482850, 9915948 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000916080

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(Oct 16, 2018)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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 (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000916080.1

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

Description

The HSD17B4 c.46G>A (p.Gly16Ser) missense variant has been reported in at least five studies and has been identified in at least 29 probands with peroxisomal bifunctional enzyme deficiency, including in 26 individuals in a homozygous state and in three individuals in a compound heterozygous state (van Grunsven et al. 1998; van Grunsven et al. 1999; Ferdinandusse et al. 2006; KonkoÄ¾ovÃ¡ et al. 2015). The variant was also identified in a compound heterozygous state with a missense variant in one individual with Perrault syndrome (Demain et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.000391 in the European (non-Finnish) population of the Genome Aggregation Database. The p.Gly16Ser variant is located at a conserved residue in a loop affecting the binding site of the dehydrogenase region of the protein. Functional studies in yeast expressing the variant and wild type protein showed loss of 3-hydroxyacyl-CoA dehydrogenase activity, but did not affect the enoyl-CoA hydratase activity (van Grunsven et al. 1998). Based on the collective evidence, the p.Gly16Ser variant is classified as pathogenic for HSD17B4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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: Apr 15, 2024

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