rs765833936
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198253.3(TERT):c.601C>T(p.Arg201Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 1,594,000 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201P) has been classified as Uncertain significance.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.601C>T | p.Arg201Trp | missense_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.601C>T | p.Arg201Trp | missense_variant | 2/15 | ||
TERT | NR_149162.3 | n.680C>T | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.680C>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.601C>T | p.Arg201Trp | missense_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.601C>T | p.Arg201Trp | missense_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.601C>T | p.Arg201Trp | missense_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.601C>T | p.Arg201Trp | missense_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1441764Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1AN XY: 717272
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74378
ClinVar
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2021 | In summary, this variant has uncertain impact on TERT function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a TERT-related disease. This variant is present in population databases (rs765833936, ExAC 0.009%). This sequence change replaces arginine with tryptophan at codon 201 of the TERT protein (p.Arg201Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2022 | The p.R201W variant (also known as c.601C>T), located in coding exon 2 of the TERT gene, results from a C to T substitution at nucleotide position 601. The arginine at codon 201 is replaced by tryptophan, an amino acid with dissimilar 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