dbSNP rs147140948: CRTAP:p.Pro289Gln (chr3-33130011-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006371.5(CRTAP):c.866C>A(p.Pro289Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P289L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.12

Publications

4 publications found

Variant links:

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

CRTAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAP	NM_006371.5 link	c.866C>A	p.Pro289Gln	missense_variant	Exon 4 of 7	ENST00000320954.11	NP_006362.1	O75718
CRTAP	NM_001393363.1 link	c.866C>A	p.Pro289Gln	missense_variant	Exon 4 of 6		NP_001380292.1
CRTAP	NM_001393365.1 link	c.716C>A	p.Pro239Gln	missense_variant	Exon 3 of 6		NP_001380294.1
CRTAP	NM_001393364.1 link	c.794-2544C>A		intron_variant	Intron 3 of 5		NP_001380293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRTAP	ENST00000320954.11 link	c.866C>A	p.Pro289Gln	missense_variant	Exon 4 of 7	1	NM_006371.5	ENSP00000323696.5	O75718
CRTAP	ENST00000485310.1 link	n.460C>A		non_coding_transcript_exon_variant	Exon 4 of 5	4
CRTAP	ENST00000449224.1 link	c.794-2544C>A		intron_variant	Intron 3 of 5	2		ENSP00000409997.1	C9JP16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251476

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111374

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.1

PhyloP100

4.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.95

REVEL

Uncertain

0.35

Sift

Benign

0.070

Sift4G

Benign

0.071

Polyphen

0.88

Vest4

0.52

MutPred

0.49

Gain of catalytic residue at P289 (P = 0.0057);

MVP

0.91

MPC

0.20

ClinPred

0.65

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

gMVP

0.54

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over