rs199698527
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025099.6(CTC1):c.1564C>T(p.Arg522Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,611,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R522Q) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.1564C>T | p.Arg522Trp | missense_variant | 9/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.1564C>T | p.Arg522Trp | missense_variant | 9/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000809 AC: 20AN: 247330Hom.: 0 AF XY: 0.0000522 AC XY: 7AN XY: 134124
GnomAD4 exome AF: 0.0000849 AC: 124AN: 1459748Hom.: 0 Cov.: 34 AF XY: 0.0000744 AC XY: 54AN XY: 726092
GnomAD4 genome ? AF: 0.000394 AC: 60AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74448
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 26, 2021 | DNA sequence analysis of the CTC1 gene demonstrated a sequence change, c.1564C>T, in exon 9 that results in an amino acid change, p.Arg522Trp. This sequence change has been described in gnomAD with a frequency of 0.095% in the African/American sub-population (dbSNP rs199698527). The p.Arg522Trp change affects a highly conserved amino acid residue located in a domain of the CTC1 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg522Trp substitution. This sequence change does not appear to have been previously described in patients with CTC1-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Arg522Trp change remains unknown at this time. - |
Cerebroretinal microangiopathy with calcifications and cysts 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Mar 12, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.1564C>T (p.R522W) alteration is located in exon 9 (coding exon 9) of the CTC1 gene. This alteration results from a C to T substitution at nucleotide position 1564, causing the arginine (R) at amino acid position 522 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dyskeratosis congenita Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at