rs1444923772
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_025099.6(CTC1):c.1213delG(p.Asp405MetfsTer58) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000558 in 1,611,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CTC1
NM_025099.6 frameshift
NM_025099.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.28
Publications
2 publications found
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]
CTC1 Gene-Disease associations (from GenCC):
- cerebroretinal microangiopathy with calcifications and cysts 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
- dyskeratosis congenitaInheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- Coats plus syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 16 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 17-8235278-TC-T is Pathogenic according to our data. Variant chr17-8235278-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 434858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_025099.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CTC1 | NM_025099.6 | MANE Select | c.1213delG | p.Asp405MetfsTer58 | frameshift | Exon 8 of 23 | NP_079375.3 | ||
| CTC1 | NM_001411067.1 | c.1213delG | p.Asp405MetfsTer58 | frameshift | Exon 8 of 21 | NP_001397996.1 | |||
| CTC1 | NR_046431.2 | n.1128delG | non_coding_transcript_exon | Exon 8 of 22 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CTC1 | ENST00000651323.1 | MANE Select | c.1213delG | p.Asp405MetfsTer58 | frameshift | Exon 8 of 23 | ENSP00000498499.1 | ||
| CTC1 | ENST00000932859.1 | c.1213delG | p.Asp405MetfsTer58 | frameshift | Exon 8 of 23 | ENSP00000602918.1 | |||
| CTC1 | ENST00000968384.1 | c.1213delG | p.Asp405MetfsTer58 | frameshift | Exon 8 of 23 | ENSP00000638443.1 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152082Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152082
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459814Hom.: 0 Cov.: 32 AF XY: 0.00000689 AC XY: 5AN XY: 726196 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1459814
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
726196
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33438
American (AMR)
AF:
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26102
East Asian (EAS)
AF:
AC:
0
AN:
39668
South Asian (SAS)
AF:
AC:
0
AN:
86232
European-Finnish (FIN)
AF:
AC:
0
AN:
53192
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1110358
Other (OTH)
AF:
AC:
1
AN:
60350
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
2
3
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5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
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6
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10
<30
30-35
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>80
Age
GnomAD4 genome 0.0000197 AC: 3AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152082
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74290
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41412
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68002
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Cerebroretinal microangiopathy with calcifications and cysts 1 (1)
1
-
-
Coats plus syndrome (1)
1
-
-
Dyskeratosis congenita (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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