chr3-33114098-GGCCGCGGC-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006371.5(CRTAP):c.24_31del(p.Ala10SerfsTer148) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000409 in 1,468,558 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. A8A) has been classified as Likely benign.
Frequency
Consequence
NM_006371.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.24_31del | p.Ala10SerfsTer148 | frameshift_variant | 1/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.24_31del | p.Ala10SerfsTer148 | frameshift_variant | 1/6 | ||
CRTAP | NM_001393364.1 | c.24_31del | p.Ala10SerfsTer148 | frameshift_variant | 1/6 | ||
CRTAP | NM_001393365.1 | c.24_31del | p.Ala10SerfsTer158 | frameshift_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.24_31del | p.Ala10SerfsTer148 | frameshift_variant | 1/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.24_31del | p.Ala10SerfsTer148 | frameshift_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151920Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000127 AC: 1AN: 78708Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 45796
GnomAD4 exome AF: 0.00000380 AC: 5AN: 1316638Hom.: 0 AF XY: 0.00000308 AC XY: 2AN XY: 650154
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151920Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Nov 30, 2019 | - - |
Osteogenesis imperfecta type 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change creates a premature translational stop signal (p.Ala10Serfs*148) 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 present in population databases (rs755750808, gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 18566967). ClinVar contains an entry for this variant (Variation ID: 1070506). 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