rs771261665
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_017849.4(TMEM127):c.253A>G(p.Met85Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M85L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.253A>G | p.Met85Val | missense_variant | 3/4 | ENST00000258439.8 | |
TMEM127 | NM_001407282.1 | c.1A>G | p.Met1? | start_lost | 2/3 | ||
TMEM127 | NM_001407283.1 | c.1A>G | p.Met1? | start_lost | 2/3 | ||
TMEM127 | NM_001193304.3 | c.253A>G | p.Met85Val | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.253A>G | p.Met85Val | missense_variant | 3/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.253A>G | p.Met85Val | missense_variant | 3/4 | 1 | P1 | ||
TMEM127 | ENST00000435268.1 | c.1A>G | p.Met1? | start_lost | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251290Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135840
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727232
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 05, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 02, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2022 | The p.M85V variant (also known as c.253A>G), located in coding exon 2 of the TMEM127 gene, results from an A to G substitution at nucleotide position 253. The methionine at codon 85 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals, but not in lower vertebrates. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 85 of the TMEM127 protein (p.Met85Val). This variant is present in population databases (rs771261665, gnomAD 0.006%). This missense change has been observed in individual(s) with mesothelioma (PMID: 29625052). ClinVar contains an entry for this variant (Variation ID: 186566). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at