rs201731405
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025099.6(CTC1):āc.194A>Gā(p.Tyr65Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000472 in 1,611,094 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. Y65Y) has been classified as Likely benign.
Frequency
Consequence
NM_025099.6 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 |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.194A>G | p.Tyr65Cys | missense_variant | 2/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.194A>G | p.Tyr65Cys | missense_variant | 2/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152108Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000327 AC: 8AN: 244508Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132636
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1458868Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 725574
GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152226Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23AN XY: 74422
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 65 of the CTC1 protein (p.Tyr65Cys). This variant is present in population databases (rs201731405, gnomAD 0.01%). 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: 241579). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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