NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 19, 2021
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:: RCV002530904.2

Allele description [Variation Report for NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys)]

NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys)

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.1516C>T (p.Arg506Cys)

HGVS:

NC_000005.10:g.119525228C>T
NG_008182.1:g.77776C>T
NM_000414.4:c.1516C>TMANE SELECT
NM_001199291.3:c.1591C>T
NM_001199292.2:c.1462C>T
NM_001292027.2:c.1444C>T
NM_001292028.2:c.1096C>T
NP_000405.1:p.Arg506Cys
NP_001186220.1:p.Arg531Cys
NP_001186221.1:p.Arg488Cys
NP_001278956.1:p.Arg482Cys
NP_001278957.1:p.Arg366Cys
NC_000005.9:g.118860923C>T
NM_000414.3:c.1516C>T

Protein change:

R366C

Links:

dbSNP: rs766199971

NCBI 1000 Genomes Browser:

rs766199971

Molecular consequence:

NM_000414.4:c.1516C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199291.3:c.1591C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199292.2:c.1462C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292027.2:c.1444C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292028.2:c.1096C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003723182	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 19, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16385454, 22864515, 25967389, 28649525 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003723182

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 19, 2021)

germline

clinical testing

PubMed (4)
[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

Hydratase activities of green fluorescent protein tagged human multifunctional enzyme type 2 hydratase domain and its variants.

Tsuchida S, Kawamoto K, Endo N, Nunome K, Hamaue N, Aoki T.

J Oleo Sci. 2012;61(8):443-50.

PubMed [citation]

PMID:: 22864515

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003723182.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.1516C>T (p.R506C) alteration is located in exon 18 (coding exon 18) of the HSD17B4 gene. This alteration results from a C to T substitution at nucleotide position 1516, causing the arginine (R) at amino acid position 506 to be replaced by a cysteine (C). Based on data from the Genome Aggregation Database (gnomAD) database, the HSD17B4 c.1516C>T alteration was observed in <0.01% (4/282248) of total alleles studied. This mutation has been identified in three homozygous and one compound heterozygous individual with D-bifunctional protein deficiency (Ferdinandusse, 2006; Konkoová, 2015). Functional studies in E. coli demonstrated that this variant abolished hydratase activity (Tsuchida, 2012; Tsuchida, 2015). The p.R506C alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is 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: Mar 11, 2025

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