chr3-33114093-C-CGG
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006371.5(CRTAP):c.21_22dup(p.Ala8GlyfsTer6) variant causes a frameshift 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 Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Consequence
CRTAP
NM_006371.5 frameshift
NM_006371.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.118
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 37 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-33114093-C-CGG is Pathogenic according to our data. Variant chr3-33114093-C-CGG is described in ClinVar as [Pathogenic]. Clinvar id is 1175017.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/6 | ||
CRTAP | NM_001393364.1 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/6 | ||
CRTAP | NM_001393365.1 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.21_22dup | p.Ala8GlyfsTer6 | frameshift_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at