ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.410-2A>C

dbSNP: rs121908826
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000114829 SCV001135916 pathogenic Pheochromocytoma 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV002512592 SCV003524701 pathogenic Hereditary pheochromocytoma-paraganglioma 2023-11-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the TMEM127 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with pheochromocytoma (PMID: 20154675, 25389632). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 107). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a new termination codon (Invitae). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000114829 SCV003807873 pathogenic Pheochromocytoma 2023-02-10 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 strong, PS4 strong, PM2 moderated
OMIM RCV000000127 SCV000020270 risk factor Pheochromocytoma, susceptibility to 2010-03-01 no assertion criteria provided literature only
Familial Cancer Clinic, Veneto Institute of Oncology RCV000114829 SCV000148724 likely pathogenic - adrenal pheochromocytoma Pheochromocytoma no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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