rs370686937
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_198253.3(TERT):c.3332C>T(p.Thr1111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,611,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T1111K) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.3332C>T | p.Thr1111Met | missense_variant | 16/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.3143C>T | p.Thr1048Met | missense_variant | 15/15 | ||
TERT | NR_149162.3 | n.3040C>T | non_coding_transcript_exon_variant | 13/13 | |||
TERT | NR_149163.3 | n.3004C>T | non_coding_transcript_exon_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.3332C>T | p.Thr1111Met | missense_variant | 16/16 | 1 | NM_198253.3 | P2 | |
ENST00000666708.1 | n.289-879G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000412 AC: 10AN: 242968Hom.: 0 AF XY: 0.00000756 AC XY: 1AN XY: 132300
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459476Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 725894
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74350
ClinVar
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1111 of the TERT protein (p.Thr1111Met). This variant is present in population databases (rs370686937, gnomAD 0.02%). 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: 539203). 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 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. - |
Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 12, 2024 | - - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Molecular Oncology Research Center, Barretos Cancer Hospital | Aug 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at