ClinVar Miner

Submissions for variant NM_199334.5(THRA):c.54-1G>A

gnomAD frequency: 0.00008  dbSNP: rs199530759
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000680127 SCV000807570 uncertain significance Congenital nongoitrous hypothyroidism 6 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000896249 SCV001040331 benign not provided 2018-07-16 criteria provided, single submitter clinical testing
GeneDx RCV000896249 SCV004168998 uncertain significance not provided 2023-11-07 criteria provided, single submitter clinical testing Canonical splice site variant in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614)
PreventionGenetics, part of Exact Sciences RCV003918121 SCV004727900 uncertain significance THRA-related disorder 2023-10-19 no assertion criteria provided clinical testing The THRA c.54-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was identified in a population study of recessive conditions (Table S1, Capalbo et al 2019. PubMed ID: 31589614), but to our knowledge has not been reported in an individuals with thyroid hormone resistance phenotype. In ClinVar, few canonical splice site variants have been reported in THRA. Careful analysis of the predicted splice effect using prediction algorithms suggest this variant may result in the activation of a cryptic splice acceptor site that results in an in-frame deletion, although such predictions are not equivalent to functional evidence (Alamut Visual Plus v1.6.1). This variant is reported in 0.12% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-38233123-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.