Submissions for variant NM_000414.4(HSD17B4):c.950C>T (p.Thr317Met)

gnomAD frequency: 0.00021  dbSNP: rs150326995

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222427	SCV000271840	uncertain significance	not specified	2015-11-03	criteria provided, single submitter	clinical testing	The p.Thr342Met variant in HSD17B4 has not been previously reported in individua ls with hearing loss, Perrault syndrome or bi-functional protein deficiency. It has been identified in 0.21% (35/16512) of South Asian chromosomes (with lower f requencies in African, European and Latino chromosomes) by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP ID=rs150326995). Althou gh this variant has been seen in the general population, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr342Met variant is unc ertain.
Illumina Laboratory Services, Illumina	RCV000344886	SCV000452121	uncertain significance	Perrault syndrome 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000380697	SCV000452122	uncertain significance	Bifunctional peroxisomal enzyme deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Eurofins Ntd Llc (ga)	RCV000731627	SCV000859471	uncertain significance	not provided	2018-01-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765793	SCV000897182	uncertain significance	Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083539	SCV001026555	benign	Bifunctional peroxisomal enzyme deficiency; Perrault syndrome	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000731627	SCV001891075	benign	not provided	2020-07-28	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000731627	SCV003811251	uncertain significance	not provided	2019-01-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000731627	SCV004159256	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	HSD17B4: BS2
Natera, Inc.	RCV000380697	SCV001457294	likely benign	Bifunctional peroxisomal enzyme deficiency	2020-01-04	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532757	SCV004743191	likely benign	HSD17B4-related disorder	2022-05-28	no assertion criteria provided	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).