ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.245-2A>G

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001379227 SCV001576988 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2020-09-10 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the TMEM127 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in an individual affected with bilateral pheochromocytoma (PMID: 20154675). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMEM127 are known to be pathogenic (PMID: 20154675, 21156949). 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.

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