Variant 3-33124441-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006371.5(CRTAP):c.655G>C(p.Gly219Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CRTAP
NM_006371.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.06

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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.655G>C	p.Gly219Arg	missense_variant	Exon 3 of 7	ENST00000320954.11	NP_006362.1	O75718
CRTAP	NM_001393363.1 link	c.655G>C	p.Gly219Arg	missense_variant	Exon 3 of 6		NP_001380292.1
CRTAP	NM_001393364.1 link	c.655G>C	p.Gly219Arg	missense_variant	Exon 3 of 6		NP_001380293.1
CRTAP	NM_001393365.1 link	c.505G>C	p.Gly169Arg	missense_variant	Exon 2 of 6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRTAP	ENST00000320954.11 link	c.655G>C	p.Gly219Arg	missense_variant	Exon 3 of 7	1	NM_006371.5	ENSP00000323696.5	O75718
CRTAP	ENST00000449224.1 link	c.655G>C	p.Gly219Arg	missense_variant	Exon 3 of 6	2		ENSP00000409997.1	C9JP16
CRTAP	ENST00000485310.1 link	n.249G>C		non_coding_transcript_exon_variant	Exon 3 of 5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251482

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.38

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.058

T;D

Polyphen

1.0

D;D

Vest4

0.70

MutPred

0.28

Gain of MoRF binding (P = 0.0048);Gain of MoRF binding (P = 0.0048);

MVP

0.78

MPC

0.28

ClinPred

0.82

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over