3-33114079-T-C
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_006371.5(CRTAP):āc.2T>Cā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,306,852 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 (ā ).
Frequency
Consequence
NM_006371.5 start_lost
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.2T>C | p.Met1? | start_lost | 1/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.2T>C | p.Met1? | start_lost | 1/6 | ||
CRTAP | NM_001393364.1 | c.2T>C | p.Met1? | start_lost | 1/6 | ||
CRTAP | NM_001393365.1 | c.2T>C | p.Met1? | start_lost | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.2T>C | p.Met1? | start_lost | 1/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.2T>C | p.Met1? | start_lost | 1/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000689 AC: 9AN: 1306852Hom.: 0 Cov.: 31 AF XY: 0.00000620 AC XY: 4AN XY: 645244
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | This sequence change affects the initiator methionine of the CRTAP mRNA. The next in-frame methionine is located at codon 42. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with osteogenesis imperfecta (PMID: 17192541). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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
Publications
No publications associated with this variant yet.