NM_005869.4:c.17_20delTCCA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005869.4(CWC27):c.17_20delTCCA(p.Ile6ArgfsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CWC27
NM_005869.4 frameshift
NM_005869.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.07
Publications
0 publications found
Genes affected
CWC27 (HGNC:10664): (CWC27 spliceosome associated cyclophilin) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein peptidyl-prolyl isomerization. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]
CWC27 Gene-Disease associations (from GenCC):
- metaphyseal chondrodysplasia-retinitis pigmentosa syndromeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 32 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-64769160-ACATC-A is Pathogenic according to our data. Variant chr5-64769160-ACATC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 1441533.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005869.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CWC27 | MANE Select | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 14 | NP_005860.2 | Q6UX04-1 | ||
| CWC27 | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 13 | NP_001284573.1 | Q6UX04 | |||
| CWC27 | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 11 | NP_001284574.1 | D6REK3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CWC27 | TSL:1 MANE Select | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 14 | ENSP00000370460.2 | Q6UX04-1 | ||
| CWC27 | TSL:1 | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 11 | ENSP00000426802.1 | D6REK3 | ||
| CWC27 | c.17_20delTCCA | p.Ile6ArgfsTer11 | frameshift | Exon 1 of 13 | ENSP00000509052.1 | A0A8I5KST0 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461838Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727210 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461838
Hom.:
AF XY:
AC XY:
1
AN XY:
727210
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111982
Other (OTH)
AF:
AC:
0
AN:
60394
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
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0
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1
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (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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