rs750870974
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_017849.4(TMEM127):c.394G>T(p.Ala132Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A132T) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.394G>T | p.Ala132Ser | missense_variant | 3/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.394G>T | p.Ala132Ser | missense_variant | 3/4 | ||
TMEM127 | NM_001407282.1 | c.142G>T | p.Ala48Ser | missense_variant | 2/3 | ||
TMEM127 | NM_001407283.1 | c.142G>T | p.Ala48Ser | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.394G>T | p.Ala132Ser | missense_variant | 3/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.394G>T | p.Ala132Ser | missense_variant | 3/4 | 1 | P1 | ||
TMEM127 | ENST00000435268.1 | c.142G>T | p.Ala48Ser | missense_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 22, 2023 | This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 2130969). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 132 of the TMEM127 protein (p.Ala132Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.