Submissions for variant NM_001287491.2(TET3):c.2254C>T (p.Arg752Cys)

gnomAD frequency: 0.00008  dbSNP: rs534089911

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
SIB Swiss Institute of Bioinformatics	RCV001007566	SCV001426220	uncertain significance	Beck-Fahrner syndrome	2020-07-22	criteria provided, single submitter	curation	This variant is interpreted as a variant of uncertain significance for Beck-Fahrner syndrome, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); For recessive disorders, detected in trans with a (likely)pathogenic variant (PM3).
Ambry Genetics	RCV004030286	SCV004964555	uncertain significance	Inborn genetic diseases	2021-12-16	criteria provided, single submitter	clinical testing	The c.1849C>T (p.R617C) alteration is located in exon 1 (coding exon 1) of the TET3 gene. This alteration results from a C to T substitution at nucleotide position 1849, causing the arginine (R) at amino acid position 617 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Washington University in St. Louis	RCV001007566	SCV005045077	uncertain significance	Beck-Fahrner syndrome	2024-02-20	criteria provided, single submitter	clinical testing	The TET3 c.2254C>T (p.Arg752Cys) variant has been reported in one individual affected with Beck-Fahrner syndrome who harbored this variant and an additional variant of uncertain significance, confirmed in trans, in a compound heterozygous state (Beck DB et al., PMID: 31928709). The highest population minor allele frequency in the population database genome aggregation database (v.2.1.1) is 0.033% in the South Asian population. Computational predictors suggest that the variant does not impact TET3 function. This variant has been reported in the ClinVar database as a germline likely pathogenic variant and variant of uncertain significance by two submitters. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004697023	SCV005198772	uncertain significance	not provided	2022-11-14	criteria provided, single submitter	clinical testing
OMIM	RCV001007566	SCV001167187	pathogenic	Beck-Fahrner syndrome	2020-06-16	no assertion criteria provided	literature only
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257922	SCV001434731	likely pathogenic	TET3 deficiency		no assertion criteria provided	research