rs771590775
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The ENST00000310581.10(TERT):c.536G>T(p.Gly179Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,577,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. G179A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000310581.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.536G>T | p.Gly179Val | missense_variant | 2/16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.536G>T | p.Gly179Val | missense_variant | 2/15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.615G>T | non_coding_transcript_exon_variant | 2/13 | ||||
TERT | NR_149163.3 | n.615G>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.536G>T | p.Gly179Val | missense_variant | 2/16 | 1 | NM_198253.3 | ENSP00000309572 | P2 | |
TERT | ENST00000334602.10 | c.536G>T | p.Gly179Val | missense_variant | 2/15 | 1 | ENSP00000334346 | A2 | ||
TERT | ENST00000460137.6 | c.536G>T | p.Gly179Val | missense_variant, NMD_transcript_variant | 2/13 | 1 | ENSP00000425003 | |||
TERT | ENST00000656021.1 | c.536G>T | p.Gly179Val | missense_variant, NMD_transcript_variant | 2/17 | ENSP00000499759 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 34
GnomAD4 exome AF: 7.02e-7 AC: 1AN: 1425342Hom.: 0 Cov.: 35 AF XY: 0.00000141 AC XY: 1AN XY: 707944
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74380
ClinVar
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 10, 2018 | 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 sequence change replaces glycine with valine at codon 179 of the TERT protein (p.Gly179Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs771590775, ExAC 0.04%). This variant has not been reported in the literature in individuals with TERT-related disease. 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. - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 26, 2023 | The p.G179V variant (also known as c.536G>T), located in coding exon 2 of the TERT gene, results from a G to T substitution at nucleotide position 536. The glycine at codon 179 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at