ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.101C>T (p.Ala34Val)

gnomAD frequency: 0.00001  dbSNP: rs587777442
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001092766 SCV001249419 pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001810425 SCV002060219 uncertain significance Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1 2021-11-08 criteria provided, single submitter clinical testing NM_000414.3(HSD17B4):c.101C>T(A34V) is a missense variant classified as a variant of uncertain significance in the context of D-bifunctional protein deficiency. A34V has been observed in cases with relevant disease (PMID: 23181892, 16385454). Functional assessments of this variant are not available in the literature. A34V has been observed in population frequency databases (gnomAD: EAS 0.01%). In summary, there is insufficient evidence to classify NM_000414.3(HSD17B4):c.101C>T(A34V) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV003764860 SCV004569794 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 34 of the HSD17B4 protein (p.Ala34Val). This variant is present in population databases (rs587777442, gnomAD 0.006%). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (PMID: 16385454, 23181892, 34719423). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 137616). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HSD17B4 protein function. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000125465 SCV000168917 pathogenic Perrault syndrome 1 2012-11-22 no assertion criteria provided literature only

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