ClinVar Miner

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

gnomAD frequency: 0.00068  dbSNP: rs201121030
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Total submissions: 4
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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 2024-07-01 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.
Mayo Clinic Laboratories, Mayo Clinic RCV003426375 SCV005412061 uncertain significance not provided 2023-09-29 criteria provided, single submitter clinical testing BP4_strong

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