ClinVar Miner

Submissions for variant NM_001953.5(TYMP):c.646+1G>A

gnomAD frequency: 0.00002  dbSNP: rs760629248
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001047337 SCV001211287 likely pathogenic not provided 2023-12-06 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the TYMP gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TYMP are known to be pathogenic (PMID: 9924029, 15781193). This variant is present in population databases (rs760629248, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with mitochondrial neurogastrointestinal encephalomyopathy (PMID: 19523753). This variant is also known as c.130G>A or IVS5+1G>A. ClinVar contains an entry for this variant (Variation ID: 844485). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV003467749 SCV004207529 pathogenic Mitochondrial DNA depletion syndrome 1 2023-11-27 criteria provided, single submitter clinical testing
GeneDx RCV001047337 SCV005201504 pathogenic not provided 2023-10-26 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 19523753)

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.