ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.1280C>T (p.Ala427Val)

gnomAD frequency: 0.00006  dbSNP: rs28943590
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000727234 SCV000603970 uncertain significance not provided 2020-03-23 criteria provided, single submitter clinical testing The p.Ala452Val variant (rs28943590) has not been reported in the medical literature, or gene specific variation databases. This variant is listed in the Exome Aggregation Consortium Browser with a Latino population frequency of 0.3 percent (identified on 33 out of 11,186 chromosomes). The alanine at position 452 is moderately conserved (considering 12 species) (Alamut v2.8.1) and computational analyses of the effects of the p.Ala452Val variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Ala452Val variant with certainty.
Invitae RCV001083581 SCV000636108 likely benign Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2024-01-25 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727234 SCV000706824 uncertain significance not provided 2018-02-13 criteria provided, single submitter clinical testing
GeneDx RCV000727234 SCV000727311 benign not provided 2020-10-28 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28649525, 22864515)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000506112 SCV001365869 uncertain significance not specified 2019-08-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala452Val variant in HSD17B4 has not been previously reported in individuals with Perrault syndrome, but has been identified in 0.2% (83/35360) of Latino chromosomes by gnomAD ( Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of this variant is uncertain, its frequency suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
PreventionGenetics, part of Exact Sciences RCV004541583 SCV004776417 likely benign HSD17B4-related disorder 2022-07-08 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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