3-33130033-C-A

Variant names:

• chr3-33130033-C-A
• rs13637
• NM_006371.5:c.888C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_006371.5(CRTAP):​c.888C>A​(p.Thr296Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T296T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CRTAP NM_006371.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.928
• Publications: 0 publications found

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]

CRTAP Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 7

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP6: Variant 3-33130033-C-A is Benign according to our data. Variant chr3-33130033-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2856019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.928 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAP	NM_006371.5	c.888C>A	p.Thr296Thr	synonymous_variant	Exon 4 of 7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1	c.888C>A	p.Thr296Thr	synonymous_variant	Exon 4 of 6		NP_001380292.1
CRTAP	NM_001393365.1	c.738C>A	p.Thr246Thr	synonymous_variant	Exon 3 of 6		NP_001380294.1
CRTAP	NM_001393364.1	c.794-2522C>A		intron_variant	Intron 3 of 5		NP_001380293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11	c.888C>A	p.Thr296Thr	synonymous_variant	Exon 4 of 7	1	NM_006371.5	ENSP00000323696.5
CRTAP	ENST00000485310.1	n.482C>A		non_coding_transcript_exon_variant	Exon 4 of 5	4
CRTAP	ENST00000449224.1	c.794-2522C>A		intron_variant	Intron 3 of 5	2		ENSP00000409997.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Osteogenesis imperfecta type 7 Benign:1

Apr 14, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	9.5
DANN	Benign	0.71
PhyloP100		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13637; hg19: chr3-33171525;