rs1060503000
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198253.3(TERT):c.82G>C(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. V28G) 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.82G>C | p.Val28Leu | missense_variant | 1/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.82G>C | p.Val28Leu | missense_variant | 1/15 | ||
TERT | NR_149162.3 | n.161G>C | non_coding_transcript_exon_variant | 1/13 | |||
TERT | NR_149163.3 | n.161G>C | non_coding_transcript_exon_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.82G>C | p.Val28Leu | missense_variant | 1/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.82G>C | p.Val28Leu | missense_variant | 1/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.82G>C | p.Val28Leu | missense_variant, NMD_transcript_variant | 1/13 | 1 | |||
TERT | ENST00000656021.1 | c.82G>C | p.Val28Leu | missense_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 34
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 23, 2023 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 28 of the TERT protein (p.Val28Leu). This variant is not present in population databases (gnomAD no frequency). 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: 410668). 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 not 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 | Jun 15, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at