rs201561504
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_025099.6(CTC1):c.2353G>A(p.Glu785Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,613,042 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00056 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 23 hom. )
Consequence
CTC1
NM_025099.6 missense
NM_025099.6 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 2.64
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0074543357).
BP6
?
Variant 17-8231935-C-T is Benign according to our data. Variant chr17-8231935-C-T is described in ClinVar as [Benign]. Clinvar id is 459596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000565 (86/152320) while in subpopulation SAS AF= 0.0172 (83/4828). AF 95% confidence interval is 0.0142. There are 3 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.2353G>A | p.Glu785Lys | missense_variant | 13/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.2353G>A | p.Glu785Lys | missense_variant | 13/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000578 AC: 88AN: 152202Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00206 AC: 508AN: 247166Hom.: 10 AF XY: 0.00286 AC XY: 384AN XY: 134196
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GnomAD4 exome AF: 0.00101 AC: 1477AN: 1460722Hom.: 23 Cov.: 33 AF XY: 0.00150 AC XY: 1088AN XY: 726666
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GnomAD4 genome ? AF: 0.000565 AC: 86AN: 152320Hom.: 3 Cov.: 32 AF XY: 0.000832 AC XY: 62AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dyskeratosis congenita Benign:2
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Cerebroretinal microangiopathy with calcifications and cysts 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at E785 (P = 0.0054);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at