rs756628621
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_198253.3(TERT):c.3352G>T(p.Ala1118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,822 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 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.3352G>T | p.Ala1118Ser | missense_variant | 16/16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.3163G>T | p.Ala1055Ser | missense_variant | 15/15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.3060G>T | non_coding_transcript_exon_variant | 13/13 | ||||
TERT | NR_149163.3 | n.3024G>T | non_coding_transcript_exon_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.3352G>T | p.Ala1118Ser | missense_variant | 16/16 | 1 | NM_198253.3 | ENSP00000309572.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459822Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726118
GnomAD4 genome Cov.: 33
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 | Feb 09, 2021 | 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. 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. This variant has not been reported in the literature in individuals with TERT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 1118 of the TERT protein (p.Ala1118Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2022 | The p.A1118S variant (also known as c.3352G>T), located in coding exon 16 of the TERT gene, results from a G to T substitution at nucleotide position 3352. The alanine at codon 1118 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.