17-8238556-CACT-CACTACT
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_025099.6(CTC1):c.268_270dupAGT(p.Ser90dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CTC1
NM_025099.6 conservative_inframe_insertion
NM_025099.6 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.335
Publications
0 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):
- dyskeratosis congenitaInheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
- cerebroretinal microangiopathy with calcifications and cysts 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Coats plus syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_025099.6. Strenght limited to Supporting due to length of the change: 1aa.
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.268_270dupAGT | p.Ser90dup | conservative_inframe_insertion | Exon 3 of 23 | NP_079375.3 | ||
| CTC1 | NM_001411067.1 | c.268_270dupAGT | p.Ser90dup | conservative_inframe_insertion | Exon 3 of 21 | NP_001397996.1 | J3KSZ1 | ||
| CTC1 | NR_046431.2 | n.288_290dupAGT | non_coding_transcript_exon | Exon 3 of 22 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CTC1 | ENST00000651323.1 | MANE Select | c.268_270dupAGT | p.Ser90dup | conservative_inframe_insertion | Exon 3 of 23 | ENSP00000498499.1 | Q2NKJ3-1 | |
| CTC1 | ENST00000932859.1 | c.268_270dupAGT | p.Ser90dup | conservative_inframe_insertion | Exon 3 of 23 | ENSP00000602918.1 | |||
| CTC1 | ENST00000968384.1 | c.268_270dupAGT | p.Ser90dup | conservative_inframe_insertion | Exon 3 of 23 | ENSP00000638443.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249282 AF XY: 0.00000740 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249282
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727216 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461840
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727216
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111986
Other (OTH)
AF:
AC:
1
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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