rs201879837
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_025099.6(CTC1):c.2307G>T(p.Trp769Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 1,609,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. W769R) has been classified as Uncertain significance.
Frequency
Consequence
NM_025099.6 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.2307G>T | p.Trp769Cys | missense_variant | 13/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.2307G>T | p.Trp769Cys | missense_variant | 13/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000865 AC: 21AN: 242774Hom.: 0 AF XY: 0.000121 AC XY: 16AN XY: 132022
GnomAD4 exome AF: 0.0000364 AC: 53AN: 1456882Hom.: 0 Cov.: 33 AF XY: 0.0000469 AC XY: 34AN XY: 724726
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 769 of the CTC1 protein (p.Trp769Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CTC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 326073). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Cerebroretinal microangiopathy with calcifications and cysts 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at