ClinVar Miner

Submissions for variant NM_001039876.3(SYNE4):c.972+5G>A

gnomAD frequency: 0.00001  dbSNP: rs369269989
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000599744 SCV000711653 uncertain significance not specified 2017-07-05 criteria provided, single submitter clinical testing The c.972+5G>A variant in SYNE4 has not been previously reported in individuals with hearing loss, but has been identified in 5/111676 European chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs369269989). Although this variant has been seen in the general population, it s frequency is not high enough to rule out a pathogenic role. This variant is lo cated in the 5' splice region. Computational tools do not suggest an impact to s plicing. However, this information is not predictive enough to rule out pathogen icity. In summary, the clinical significance of the c.972+5G>A variant is uncert ain.
Athena Diagnostics RCV000993229 SCV001146045 likely benign not provided 2018-11-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000993229 SCV005830562 uncertain significance not provided 2024-09-23 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the SYNE4 gene. It does not directly change the encoded amino acid sequence of the SYNE4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369269989, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SYNE4-related conditions. ClinVar contains an entry for this variant (Variation ID: 504861). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.