ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.1704T>A (p.Tyr568Ter)

gnomAD frequency: 0.00001  dbSNP: rs1038744864
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000811384 SCV000951649 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2023-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr568*) in the HSD17B4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454, 20673864). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Perrault syndrome (PMID: 20673864). ClinVar contains an entry for this variant (Variation ID: 655256). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001260323 SCV001437248 pathogenic Bifunctional peroxisomal enzyme deficiency 2020-09-17 criteria provided, single submitter clinical testing Variant summary: HSD17B4 c.1704T>A (p.Tyr568X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250998 control chromosomes (gnomAD). c.1704T>A has been reported in the literature in individuals affected with Perrault syndrome (Pierce_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001556667 SCV001778289 pathogenic not provided 2021-01-11 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20673864, 27650058, 22037954, 26243799, 27790638, 28017249, 28830375, 31455392)
Revvity Omics, Revvity RCV001556667 SCV003825245 pathogenic not provided 2021-12-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV001260323 SCV004192378 pathogenic Bifunctional peroxisomal enzyme deficiency 2023-10-02 criteria provided, single submitter clinical testing
OMIM RCV000023153 SCV000044444 pathogenic Perrault syndrome 1 2010-08-13 no assertion criteria provided literature only
Natera, Inc. RCV001260323 SCV002075425 pathogenic Bifunctional peroxisomal enzyme deficiency 2021-08-11 no assertion criteria provided clinical testing
GeneReviews RCV002538095 SCV003525951 not provided Perrault syndrome no assertion provided literature only

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