rs558802130
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_025099.6(CTC1):c.2472C>T(p.Pro824=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,304 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
CTC1
NM_025099.6 synonymous
NM_025099.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0660
Genes affected
CTC1 (HGNC:26169): (CST telomere replication complex component 1) This gene encodes a component of the CST complex. This complex plays an essential role in protecting telomeres from degradation. This protein also forms a heterodimer with the CST complex subunit STN1 to form the enzyme alpha accessory factor. This enzyme regulates DNA replication. Mutations in this gene are the cause of cerebroretinal microangiopathy with calcifications and cysts. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 17-8231729-G-A is Benign according to our data. Variant chr17-8231729-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 891173.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BP7
Synonymous conserved (PhyloP=0.066 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.2472C>T | p.Pro824= | synonymous_variant | 14/23 | ENST00000651323.1 | NP_079375.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.2472C>T | p.Pro824= | synonymous_variant | 14/23 | NM_025099.6 | ENSP00000498499 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249462Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135368
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461052Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11AN XY: 726852
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74444
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Dyskeratosis congenita Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 14, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 21, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at