2-96265246-T-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_017849.4(TMEM127):āc.136A>Gā(p.Thr46Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,595,470 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T46S) has been classified as Uncertain significance.
Frequency
Consequence
NM_017849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM127 | NM_017849.4 | c.136A>G | p.Thr46Ala | missense_variant | 2/4 | ENST00000258439.8 | |
TMEM127 | NM_001193304.3 | c.136A>G | p.Thr46Ala | missense_variant | 2/4 | ||
TMEM127 | NM_001407283.1 | c.-9+623A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM127 | ENST00000258439.8 | c.136A>G | p.Thr46Ala | missense_variant | 2/4 | 1 | NM_017849.4 | P1 | |
TMEM127 | ENST00000432959.1 | c.136A>G | p.Thr46Ala | missense_variant | 2/4 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000470 AC: 10AN: 212656Hom.: 0 AF XY: 0.0000256 AC XY: 3AN XY: 117228
GnomAD4 exome AF: 0.0000152 AC: 22AN: 1443154Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 717190
GnomAD4 genome AF: 0.000184 AC: 28AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 10, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 18, 2023 | 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 - |
TMEM127-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 04, 2022 | The TMEM127 c.136A>G variant is predicted to result in the amino acid substitution p.Thr46Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.085% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-96930984-T-C) and has conflicting interpretations of likely benign and uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/463838/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Pheochromocytoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 21, 2024 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The p.T46A variant (also known as c.136A>G), located in coding exon 1 of the TMEM127 gene, results from an A to G substitution at nucleotide position 136. The threonine at codon 46 is replaced by alanine, 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at