rs202033269
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_198253.3(TERT):c.2744G>A(p.Gly915Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,010 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. G915S) has been classified as Uncertain significance.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2744G>A | p.Gly915Asp | missense_variant | 11/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.2654+1961G>A | intron_variant | ||||
TERT | NR_149162.3 | n.2551+1961G>A | intron_variant, non_coding_transcript_variant | ||||
TERT | NR_149163.3 | n.2515+1961G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.2744G>A | p.Gly915Asp | missense_variant | 11/16 | 1 | NM_198253.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249412Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135390
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461644Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727126
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74508
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal dominant 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 28, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 09, 2021 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 915 of the TERT protein (p.Gly915Asp). This variant is present in population databases (rs202033269, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 471875). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TERT protein function. 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. - |
TERT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 12, 2024 | The TERT c.2744G>A variant is predicted to result in the amino acid substitution p.Gly915Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of Latino descent in gnomAD. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/471875/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at