ClinVar Miner

Submissions for variant NM_001365276.2(TNXB):c.11581G>A (p.Ala3861Thr)

gnomAD frequency: 0.00068  dbSNP: rs201121030
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002278094 SCV002566191 uncertain significance Ehlers-Danlos syndrome 2021-05-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003426375 SCV004156222 likely benign not provided 2023-11-01 criteria provided, single submitter clinical testing TNXB: BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987990 SCV004804366 likely benign not specified 2024-01-10 criteria provided, single submitter clinical testing Variant summary: TNXB c.11575G>A (p.Ala3859Thr) results in a non-conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00095 in 734274 control chromosomes, predominantly at a frequency of 0.0012 within the Non-Finnish European subpopulation in the gnomAD database (v4.0.0), including 1 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is higher than the estimated maximal expected allele frequency for a pathogenic variant in TNXB causing Ehlers-Danlos-like syndrome phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.11575G>A has been reported in the literature in individuals affected with Primary Vesicoureteric Reflux (Elahi_2016). This report does not provide unequivocal conclusions about association of the variant with Ehlers-Danlos-like syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 26408188). ClinVar contains an entry for this variant (Variation ID: 1702304). Based on the evidence outlined above, the variant was classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.