ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.530del (p.Phe177fs)

dbSNP: rs1684148846
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001068692 SCV001233818 pathogenic Hereditary pheochromocytoma-paraganglioma 2023-02-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the TMEM127 protein. Other variant(s) that result in a similarly extended protein product (p.Thr191Argfs*116) have been determined to be pathogenic (PMID: 26960314, 28567294; Invitae). This suggests that these extensions are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 862047). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the TMEM127 gene (p.Phe177Serfs*130). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 62 amino acid(s) of the TMEM127 protein and extend the protein by 67 additional amino acid residues.
Ambry Genetics RCV004030685 SCV005027586 likely pathogenic Hereditary cancer-predisposing syndrome 2023-12-27 criteria provided, single submitter clinical testing The c.530delT variant, located in coding exon 3 of the TMEM127 gene, results from a deletion of one nucleotide at nucleotide position 530, causing a translational frameshift with a predicted alternate stop codon (p.F177Sfs*130). This alteration occurs at the 3' terminus of the TMEM127 gene, is not expected to trigger nonsense-mediated mRNA decay and results in the elongation of the protein by 67 amino acids. This frameshift impacts approximately the last 26% of the native protein. Frameshifts are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). Similar frameshifting elongations have been detected in individuals diagnosed with pheochromocytomas (Ambry internal data; Patócs A et al. Pathol Oncol Res 2016 Oct;22(4):673-9; Yu R et al. Endocrinol Diabetes Metab Case Rep 2017 May;2017; Armaiz-Pena G et al. J Clin Endocrinol Metab 2021 Jan;106(1):e350-e364). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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.