ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.1280C>T (p.Ala427Val) (rs28943590)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282329 SCV000603970 uncertain significance none 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 2020-12-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727234 SCV000706824 uncertain significance not provided 2018-02-13 criteria provided, single submitter clinical testing
GeneDx RCV000506112 SCV000727311 likely benign not specified 2018-02-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare 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 (http://gnomad.broadinstitute.org). 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.

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