chr5-1255344-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198253.3(TERT):c.3100C>T(p.Arg1034Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1034H) has been classified as Uncertain significance.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
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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.3100C>T | p.Arg1034Cys | missense_variant | 14/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.2911C>T | p.Arg971Cys | missense_variant | 13/15 | ||
TERT | NR_149162.3 | n.2808C>T | non_coding_transcript_exon_variant | 11/13 | |||
TERT | NR_149163.3 | n.2772C>T | non_coding_transcript_exon_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.3100C>T | p.Arg1034Cys | missense_variant | 14/16 | 1 | NM_198253.3 | P2 | |
ENST00000666708.1 | n.387G>A | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249210Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135342
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727232
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 13, 2017 | - - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1034 of the TERT protein (p.Arg1034Cys). This variant is present in population databases (rs777672180, gnomAD 0.0009%). This missense change has been observed in individual(s) with familial pulmonary fibrosis (PMID: 29382801). ClinVar contains an entry for this variant (Variation ID: 436984). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TERT protein function. Experimental studies have shown that this missense change affects TERT function (PMID: 29382801). 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