17-8238579-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025099.6(CTC1):c.248G>A(p.Ser83Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S83T) 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.248G>A | p.Ser83Asn | missense_variant | 3/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.248G>A | p.Ser83Asn | missense_variant | 3/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152178Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248724Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134918
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461548Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727074
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74332
ClinVar
Submissions by phenotype
Cerebroretinal microangiopathy with calcifications and cysts 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 83 of the CTC1 protein (p.Ser83Asn). This variant is present in population databases (rs78870822, gnomAD 0.06%). 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: 803320). 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 disrupt the consensus 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