rs387907333

Positions:

• chr3-33114194-CGAGCTGATGCCGCTCG-CTACCC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_006371.5(CRTAP):​c.118_133delGAGCTGATGCCGCTCGinsTACCC​(p.Glu40fs) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CRTAP NM_006371.5 frameshift, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.38

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-33114195-GAGCTGATGCCGCTCG-TACCC is Pathogenic according to our data. Variant chr3-33114195-GAGCTGATGCCGCTCG-TACCC is described in ClinVar as [Pathogenic]. Clinvar id is 41922.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAP	NM_006371.5	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/6		NP_001380292.1
CRTAP	NM_001393364.1	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/6		NP_001380293.1
CRTAP	NM_001393365.1	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/7	1	NM_006371.5	ENSP00000323696.5
CRTAP	ENST00000449224.1	c.118_133delGAGCTGATGCCGCTCGinsTACCC	p.Glu40fs	frameshift_variant, missense_variant	1/6	2		ENSP00000409997.1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteogenesis imperfecta type 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs387907333; hg19: chr3-33155687;