3-33114090-C-CGCCGGGGG
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_006371.5(CRTAP):c.18_25dupGGGGGCCG(p.Ala9GlyfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_006371.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 7 | ENST00000320954.11 | NP_006362.1 | |
CRTAP | NM_001393363.1 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 6 | NP_001380292.1 | ||
CRTAP | NM_001393364.1 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 6 | NP_001380293.1 | ||
CRTAP | NM_001393365.1 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 6 | NP_001380294.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 7 | 1 | NM_006371.5 | ENSP00000323696.5 | ||
CRTAP | ENST00000449224.1 | c.18_25dupGGGGGCCG | p.Ala9GlyfsTer7 | frameshift_variant | Exon 1 of 6 | 2 | ENSP00000409997.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1309074Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 646252
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 7 Pathogenic:2
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This sequence change creates a premature translational stop signal (p.Ala9Glyfs*7) in the CRTAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRTAP are known to be pathogenic (PMID: 17055431, 19862557, 24715559). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive osteogenesis imperfecta (PMID: 33093841). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at