rs146536910
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_025099.6(CTC1):c.3173T>G(p.Leu1058Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L1058L) has been classified as Likely benign.
Frequency
Consequence
NM_025099.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.3173T>G | p.Leu1058Arg | missense_variant | 20/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.3173T>G | p.Leu1058Arg | missense_variant | 20/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000641 AC: 16AN: 249546Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135388
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727240
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74506
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2023 | The c.3173T>G (p.L1058R) alteration is located in exon 20 (coding exon 20) of the CTC1 gene. This alteration results from a T to G substitution at nucleotide position 3173, causing the leucine (L) at amino acid position 1058 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1058 of the CTC1 protein (p.Leu1058Arg). This variant is present in population databases (rs146536910, gnomAD 0.1%). 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: 459600). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at