ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.245-1G>C

gnomAD frequency: 0.00004  dbSNP: rs121908821
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
Invitae RCV000692290 SCV000820104 pathogenic Hereditary pheochromocytoma-paraganglioma 2023-07-06 criteria provided, single submitter clinical testing Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 571215). Disruption of this splice site has been observed in individual(s) with bilateral pheochromocytoma (PMID: 20154675). This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change affects an acceptor splice site in intron 2 of the TMEM127 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001015587 SCV001176436 pathogenic Hereditary cancer-predisposing syndrome 2023-10-26 criteria provided, single submitter clinical testing The c.245-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 2 of the TMEM127 gene. This alteration has been reported in individuals with personal history of pheochromocytoma (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
New York Genome Center RCV001420569 SCV001622881 likely pathogenic Pheochromocytoma 2020-06-19 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001015587 SCV002527244 likely pathogenic Hereditary cancer-predisposing syndrome 2021-08-17 criteria provided, single submitter curation

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.