ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.67C>T (p.Arg23Ter)

dbSNP: rs765702241
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411032 SCV000487227 likely pathogenic Bifunctional peroxisomal enzyme deficiency 2016-11-04 criteria provided, single submitter clinical testing
Invitae RCV001861399 SCV002187571 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2023-06-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371607). This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. This variant is present in population databases (rs765702241, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg23*) 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).
Ambry Genetics RCV002523882 SCV003553018 likely pathogenic Inborn genetic diseases 2020-12-08 criteria provided, single submitter clinical testing The c.67C>T (p.R23*) alteration, located in exon 2 (coding exon 2) of the HSD17B4 gene, consists of a C to T substitution at nucleotide position 67. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 23. The predicted stop codon occurs within the first 150 nucleotides of the HSD17B4 gene. This alteration may escape nonsense-mediated mRNA decay and/or be rescued by re-initiation (Rivas, 2015; Lindeboom, 2016; Rhee, 2017). However, a significant portion of the protein is affected and the impacted region is critical for protein function (Ambry internal data). In addition, other 5' frameshift truncations have been reported in patients with peroxisomal D-bifunctional protein (DBP) deficiency (Amor, 2016). Based on data from the Genome Aggregation Database (gnomAD) database, the HSD17B4 c.67C>T alteration was observed in 0.0008% (2/251,446) of total alleles studied, with a frequency of 0.006% (1/16,256) in the African subpopulation. Based on the available evidence, this alteration is classified as likely pathogenic.
Baylor Genetics RCV000411032 SCV004192397 likely pathogenic Bifunctional peroxisomal enzyme deficiency 2023-06-11 criteria provided, single submitter clinical testing

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