rs773366454
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The ENST00000310581.10(TERT):c.1025G>A(p.Arg342Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,546,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R342W) 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.1025G>A | p.Arg342Gln | missense_variant | 2/16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.1025G>A | p.Arg342Gln | missense_variant | 2/15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.1104G>A | non_coding_transcript_exon_variant | 2/13 | ||||
TERT | NR_149163.3 | n.1104G>A | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.1025G>A | p.Arg342Gln | missense_variant | 2/16 | 1 | NM_198253.3 | ENSP00000309572 | P2 | |
TERT | ENST00000334602.10 | c.1025G>A | p.Arg342Gln | missense_variant | 2/15 | 1 | ENSP00000334346 | A2 | ||
TERT | ENST00000460137.6 | c.1025G>A | p.Arg342Gln | missense_variant, NMD_transcript_variant | 2/13 | 1 | ENSP00000425003 | |||
TERT | ENST00000656021.1 | c.1025G>A | p.Arg342Gln | missense_variant, NMD_transcript_variant | 2/17 | ENSP00000499759 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1393834Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1AN XY: 687796
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3AN XY: 74328
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 02, 2022 | The p.R342Q variant (also known as c.1025G>A), located in coding exon 2 of the TERT gene, results from a G to A substitution at nucleotide position 1025. The arginine at codon 342 is replaced by glutamine, an amino acid with highly similar 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. - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at