NM_006371.5:c.18_25delGGGGGCCG
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006371.5(CRTAP):c.18_25delGGGGGCCG(p.Ala10SerfsTer148) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000306 in 1,309,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000031 ( 0 hom. )
Consequence
CRTAP
NM_006371.5 frameshift
NM_006371.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.06
Publications
0 publications found
Genes affected
CRTAP (HGNC:2379): (cartilage associated protein) The protein encoded by this gene is similar to the chicken and mouse CRTAP genes. The encoded protein is a scaffolding protein that may influence the activity of at least one member of the cytohesin/ARNO family in response to specific cellular stimuli. Defects in this gene are associated with osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility and low bone mass. [provided by RefSeq, Jul 2008]
CRTAP Gene-Disease associations (from GenCC):
- osteogenesis imperfecta type 7Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- osteogenesis imperfecta type 2Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 3Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 4Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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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 54 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-33114090-CGCCGGGGG-C is Pathogenic according to our data. Variant chr3-33114090-CGCCGGGGG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2633856.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006371.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CRTAP | NM_006371.5 | MANE Select | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 7 | NP_006362.1 | O75718 | |
| CRTAP | NM_001393363.1 | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 6 | NP_001380292.1 | |||
| CRTAP | NM_001393364.1 | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 6 | NP_001380293.1 | C9JP16 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CRTAP | ENST00000320954.11 | TSL:1 MANE Select | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 7 | ENSP00000323696.5 | O75718 | |
| CRTAP | ENST00000946650.1 | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 7 | ENSP00000616709.1 | |||
| CRTAP | ENST00000946648.1 | c.18_25delGGGGGCCG | p.Ala10SerfsTer148 | frameshift | Exon 1 of 7 | ENSP00000616707.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome AF: 0.00000306 AC: 4AN: 1309076Hom.: 0 AF XY: 0.00000619 AC XY: 4AN XY: 646254 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1309076
Hom.:
AF XY:
AC XY:
4
AN XY:
646254
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26216
American (AMR)
AF:
AC:
0
AN:
23446
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22548
East Asian (EAS)
AF:
AC:
0
AN:
28702
South Asian (SAS)
AF:
AC:
0
AN:
70894
European-Finnish (FIN)
AF:
AC:
0
AN:
32872
Middle Eastern (MID)
AF:
AC:
0
AN:
4510
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1045748
Other (OTH)
AF:
AC:
0
AN:
54140
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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8
10
<30
30-35
35-40
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
CRTAP-related disorder (1)
1
-
-
Osteogenesis imperfecta type 7 (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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