5-1279410-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PM5PP5BP4
The NM_198253.3(TERT):c.2011C>G(p.Arg671Gly) 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. 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. R671W) has been classified as Pathogenic.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2011C>G | p.Arg671Gly | missense_variant | Exon 5 of 16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.2011C>G | p.Arg671Gly | missense_variant | Exon 5 of 15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.2090C>G | non_coding_transcript_exon_variant | Exon 5 of 13 | ||||
TERT | NR_149163.3 | n.2090C>G | non_coding_transcript_exon_variant | Exon 5 of 13 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita Pathogenic:1
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Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
This variant has not been reported in the literature in individuals with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 436994). This sequence change replaces arginine with glycine at codon 671 of the TERT protein (p.Arg671Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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