NM_000414.4(HSD17B4):c.163G>A (p.Ala55Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 2023
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:: RCV002012223.3

Allele description [Variation Report for NM_000414.4(HSD17B4):c.163G>A (p.Ala55Thr)]

NM_000414.4(HSD17B4):c.163G>A (p.Ala55Thr)

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.163G>A (p.Ala55Thr)

HGVS:

NC_000005.10:g.119473958G>A
NG_008182.1:g.26506G>A
NM_000414.4:c.163G>AMANE SELECT
NM_001199291.3:c.238G>A
NM_001199292.2:c.109G>A
NM_001292027.2:c.91G>A
NM_001292028.2:c.-249G>A
NM_001374497.1:c.163G>A
NM_001374498.1:c.163G>A
NM_001374499.1:c.-118G>A
NM_001374500.1:c.-376G>A
NM_001374501.1:c.-249G>A
NM_001374502.1:c.-254G>A
NM_001374503.1:c.-254G>A
NP_000405.1:p.Ala55Thr
NP_001186220.1:p.Ala80Thr
NP_001186221.1:p.Ala37Thr
NP_001278956.1:p.Ala31Thr
NP_001361426.1:p.Ala55Thr
NP_001361427.1:p.Ala55Thr
NC_000005.9:g.118809653G>A
NR_164653.1:n.242G>A
NR_164654.1:n.430G>A

Protein change:

A31T

Links:

dbSNP: rs780149071

NCBI 1000 Genomes Browser:

rs780149071

Molecular consequence:

NM_001292028.2:c.-249G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374499.1:c.-118G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374500.1:c.-376G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374501.1:c.-249G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374502.1:c.-254G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374503.1:c.-254G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000414.4:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199291.3:c.238G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199292.2:c.109G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001292027.2:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374497.1:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374498.1:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164653.1:n.242G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164654.1:n.430G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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unnamed protein product [Mus musculus]
unnamed protein product [Mus musculus]
gi|74183107|dbj|BAE22518.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002234933	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002234933

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

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

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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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002234933.3

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 55 of the HSD17B4 protein (p.Ala55Thr). This variant is present in population databases (rs780149071, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1448723). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 5, 2024

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