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NM_000414.4(HSD17B4):c.743G>A (p.Arg248His) AND HSD17B4-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 16, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_000414.4(HSD17B4):c.743G>A (p.Arg248His)]

NM_000414.4(HSD17B4):c.743G>A (p.Arg248His)

HSD17B4:hydroxysteroid 17-beta dehydrogenase 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000414.4(HSD17B4):c.743G>A (p.Arg248His)
  • NC_000005.10:g.119493821G>A
  • NG_008182.1:g.46369G>A
  • NM_000414.4:c.743G>AMANE SELECT
  • NM_001199291.3:c.818G>A
  • NM_001199292.2:c.689G>A
  • NM_001292027.2:c.671G>A
  • NM_001292028.2:c.323G>A
  • NP_000405.1:p.Arg248His
  • NP_001186220.1:p.Arg273His
  • NP_001186221.1:p.Arg230His
  • NP_001278956.1:p.Arg224His
  • NP_001278957.1:p.Arg108His
  • NC_000005.9:g.118829516G>A
  • NM_000414.3:c.743G>A
Protein change:
dbSNP: rs748057401
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000414.4:c.743G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199291.3:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199292.2:c.689G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001292027.2:c.671G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001292028.2:c.323G>A - missense variant - [Sequence Ontology: SO:0001583]


HSD17B4-related disorder
HSD17B4-Related Disorders; HSD17B4-related condition

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV004765905PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 16, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004765905.1

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


The HSD17B4 c.743G>A variant is predicted to result in the amino acid substitution p.Arg248His. This variant was reported in a compound heterozygous individual with a mitochondrial disorder (Family 66, Table 2, Schon et al 2021. PubMed ID: 34732400). A different variant impacting the same amino acid residue (p.Arg248Cys) has been reported in the homozygous and compound heterozygous state in individuals with D-bifunctional protein deficiency (Mehtälä et al. 2013. PubMed ID: 23308274; Ferdinandusse et al. 2005. PubMed ID: 16385454). This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. While this variant could be pathogenic, at this time its clinical significance is interpreted as uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Jul 15, 2024