rs72659361
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006371.5(CRTAP):c.826C>T(p.Gln276Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006371.5 stop_gained
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.826C>T | p.Gln276Ter | stop_gained | 4/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.826C>T | p.Gln276Ter | stop_gained | 4/6 | ||
CRTAP | NM_001393365.1 | c.676C>T | p.Gln226Ter | stop_gained | 3/6 | ||
CRTAP | NM_001393364.1 | c.794-2584C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.826C>T | p.Gln276Ter | stop_gained | 4/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.794-2584C>T | intron_variant | 2 | |||||
CRTAP | ENST00000485310.1 | n.420C>T | non_coding_transcript_exon_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152164Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251460Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135902
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460886Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726828
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152282Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 9AN XY: 74456
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 7 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Feb 14, 2022 | ACMG classification criteria: PVS1 very strong, PS4 supporting, PM2 moderate, PM3 supporting - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change creates a premature translational stop signal (p.Gln276*) 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 (rs72659361, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 17192541). ClinVar contains an entry for this variant (Variation ID: 4950). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2012 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 12, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect on the protein resulting in nonsense mediated decay (Barnes et al. 2006); This variant is associated with the following publications: (PMID: 22344438, 19846465, 20981092, 25525159, 17192541, 29620724, 19878741, 33726816, 23054245) - |
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Sep 04, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at