Submissions for variant NM_002772.3(TMPRSS15):c.2135C>G (p.Ser712Ter)

gnomAD frequency: 0.00064  dbSNP: rs77200626

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522000	SCV000616897	pathogenic	not provided	2023-10-12	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; This variant is associated with the following publications: (PMID: 20981092, 11719902, 22344438, 29431110, 1147667, 31980526, 31589614)
Invitae	RCV000522000	SCV001418981	pathogenic	not provided	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser712*) in the TMPRSS15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMPRSS15 are known to be pathogenic (PMID: 11719902). This variant is present in population databases (rs77200626, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with congenital enteropeptidase deficiency (PMID: 11719902). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4164). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000004381	SCV001440221	uncertain significance	Enterokinase deficiency	2019-01-01	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous.
Genetic Diagnostics Department, Viafet Genomics Laboratory	RCV000004381	SCV001976441	pathogenic	Enterokinase deficiency	2021-08-23	criteria provided, single submitter	clinical testing	As part of Carrier Screening testing performed at Viafet Genomics Laboratory, this variant was identified in a heterozygous state in a patient who is not affected with this condition. This variant is present in exon 18/25 in the only transcript of this gene. Several loss-of-function variants are reported as disease-causing in HGMD and/or ClinVar after this position. Holzinger et al., 2002 have identified this variant in a compound heterozygous state in 2 siblings affected with Enterokinase deficiency (PMID: 11719902).
Revvity Omics, Revvity	RCV000004381	SCV002022354	pathogenic	Enterokinase deficiency	2022-01-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000522000	SCV004151040	pathogenic	not provided	2022-10-01	criteria provided, single submitter	clinical testing	TMPRSS15: PVS1, PM3, PM2:Supporting
Genetics and Molecular Pathology, SA Pathology	RCV000004381	SCV004175251	pathogenic	Enterokinase deficiency	2022-07-08	criteria provided, single submitter	clinical testing	The TMPRSS15 c.2135C>G variant is classified as Pathogenic (PVS1, PM2, PP1) The TMPRSS15 c.2135C>G variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 712. The variant is rare in population databases (gnomAD allele frequency = 0.064%; 98 het and 0 hom in 152120 sequenced alleles; highest frequency = 0.11%, Non-Finnish European population) (PM2). This variant has been reported to segregate with congenital enteropeptidase deficiency in a family with 2 affected siblings (PMID: 11719902) ); PP1). The variant has been reported in dbSNP (rs77200626) and has been reported with Conflicting interpretations of pathogenicity by other diagnostic laboratories (ClinVar Variation ID: 4164). It has not been reported in HGMD.
OMIM	RCV000004381	SCV000024553	pathogenic	Enterokinase deficiency	2002-01-01	no assertion criteria provided	literature only