rs369255297
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025099.6(CTC1):c.2611G>A(p.Val871Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,608,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 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. V871V) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.2611G>A | p.Val871Met | missense_variant | 15/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.2611G>A | p.Val871Met | missense_variant | 15/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248160Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134714
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1456070Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3AN XY: 723186
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
Cerebroretinal microangiopathy with calcifications and cysts 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 22, 2012 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 13, 2021 | 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. This variant has been reported to have conflicting or insufficient data to determine the effect on CTC1 protein function (PMID: 24115768, 29228254, 29481669, 23869908). This variant has been observed in individual(s) with Coats plus syndrome (PMID: 22267198). This variant is also known as V866M in the literature. ClinVar contains an entry for this variant (Variation ID: 30997). This variant is present in population databases (rs369255297, ExAC 0.05%). This sequence change replaces valine with methionine at codon 871 of the CTC1 protein (p.Val871Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at