rs144659242
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017849.4(TMEM127):c.136A>T(p.Thr46Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T46A) has been classified as Likely benign.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.136A>T | p.Thr46Ser | missense_variant | 2/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.136A>T | p.Thr46Ser | missense_variant | 2/4 | ||
TMEM127 | NM_001407283.1 | c.-9+623A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.136A>T | p.Thr46Ser | missense_variant | 2/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.136A>T | p.Thr46Ser | missense_variant | 2/4 | 1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2019 | The p.T46S variant (also known as c.136A>T), located in coding exon 1 of the TMEM127 gene, results from an A to T substitution at nucleotide position 136. The threonine at codon 46 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Aug 07, 2021 | This sequence change replaces threonine with serine at codon 46 of the TMEM127 protein (p.Thr46Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TMEM127-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at