ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.1528G>A (p.Asp510Asn)

gnomAD frequency: 0.00002  dbSNP: rs191468413
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414223 SCV000491075 likely pathogenic not provided 2023-03-19 criteria provided, single submitter clinical testing Reported with a second HSD17B4 variant on the opposite allele (in trans) in a patient with progressive spasticity, abnormality of peripheral nerve conduction, and developmental regression in the published literature (Barbosa-Gouveia et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34440436)
Eurofins Ntd Llc (ga) RCV000414223 SCV000858413 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing
Invitae RCV001314566 SCV001505102 uncertain significance Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 510 of the HSD17B4 protein (p.Asp510Asn). This variant is present in population databases (rs191468413, gnomAD 0.009%). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (PMID: 34440436). ClinVar contains an entry for this variant (Variation ID: 372681). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.