ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.427G>A (p.Val143Ile)

gnomAD frequency: 0.00002  dbSNP: rs772153618
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538062 SCV000637922 uncertain significance Hereditary pheochromocytoma-paraganglioma 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 143 of the TMEM127 protein (p.Val143Ile). This variant is present in population databases (rs772153618, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. ClinVar contains an entry for this variant (Variation ID: 463847). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000764449 SCV000895510 uncertain significance Pheochromocytoma 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022205 SCV001183913 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-31 criteria provided, single submitter clinical testing The p.V143I variant (also known as c.427G>A), located in coding exon 3 of the TMEM127 gene, results from a G to A substitution at nucleotide position 427. The valine at codon 143 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000764449 SCV004206165 uncertain significance Pheochromocytoma 2023-08-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478153 SCV004221328 uncertain significance not provided 2023-02-17 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000023 (3/128968 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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