NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys) AND Bifunctional peroxisomal enzyme deficiency

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000590157.5

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:: Bifunctional peroxisomal enzyme deficiency (DBIF)
Synonyms:: DBP DEFICIENCY; PBFE DEFICIENCY; D-bifunctional protein deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009855; MedGen: C0342870; OMIM: 261515

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696690	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 16, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16385454, 25967389 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001132227	Counsyl	no assertion criteria provided	Likely pathogenic (Oct 8, 2018)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16385454, 22864515, 25967389
SCV001458667	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV004192379	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 21, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696690.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The HSD17B4 c.1516C>T (p.Arg506Cys) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 2/120420 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic HSD17B4 variant (0.002958). The variant has been reported in affected individuals in the literature both in the homozygous and compound heterozygous state. Additionally, functional studies have shown the variant to abolish hydratase activity (Tsuchida_2015). Taken together, this variant 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

From Counsyl, SCV001132227.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001458667.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Baylor Genetics, SCV004192379.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 11, 2025

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