rs1060503013
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198253.3(TERT):c.146C>T(p.Ala49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A49G) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.146C>T | p.Ala49Val | missense_variant | 1/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.146C>T | p.Ala49Val | missense_variant | 1/15 | ||
TERT | NR_149162.3 | n.225C>T | non_coding_transcript_exon_variant | 1/13 | |||
TERT | NR_149163.3 | n.225C>T | non_coding_transcript_exon_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.146C>T | p.Ala49Val | missense_variant | 1/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.146C>T | p.Ala49Val | missense_variant | 1/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.146C>T | p.Ala49Val | missense_variant, NMD_transcript_variant | 1/13 | 1 | |||
TERT | ENST00000656021.1 | c.146C>T | p.Ala49Val | missense_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000535 AC: 7AN: 1308016Hom.: 0 Cov.: 34 AF XY: 0.00000777 AC XY: 5AN XY: 643388
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74406
ClinVar
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2023 | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 49 of the TERT protein (p.Ala49Val). 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: 410695). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at