rs756818796
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_017849.4(TMEM127):c.619G>A(p.Ala207Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A207A) has been classified as Benign.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.619G>A | p.Ala207Thr | missense_variant | 4/4 | ENST00000258439.8 | NP_060319.1 | |
TMEM127 | NM_001193304.3 | c.619G>A | p.Ala207Thr | missense_variant | 4/4 | NP_001180233.1 | ||
TMEM127 | NM_001407282.1 | c.367G>A | p.Ala123Thr | missense_variant | 3/3 | NP_001394211.1 | ||
TMEM127 | NM_001407283.1 | c.367G>A | p.Ala123Thr | missense_variant | 3/3 | NP_001394212.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.619G>A | p.Ala207Thr | missense_variant | 4/4 | 1 | NM_017849.4 | ENSP00000258439 | P1 | |
TMEM127 | ENST00000432959.1 | c.619G>A | p.Ala207Thr | missense_variant | 4/4 | 1 | ENSP00000416660 | P1 | ||
TMEM127 | ENST00000435268.1 | c.367G>A | p.Ala123Thr | missense_variant | 3/3 | 3 | ENSP00000411810 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461708Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727166
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Pheochromocytoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 04, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The p.A207T variant (also known as c.619G>A), located in coding exon 3 of the TMEM127 gene, results from a G to A substitution at nucleotide position 619. The alanine at codon 207 is replaced by threonine, 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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 207 of the TMEM127 protein (p.Ala207Thr). This variant is present in population databases (rs756818796, gnomAD 0.002%). 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: 241227). 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. 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