rs4076086

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000320954.11(CRTAP):​c.534C>G​(p.Asp178Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D178D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CRTAP
ENST00000320954.11 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.934
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAPNM_006371.5 linkuse as main transcriptc.534C>G p.Asp178Glu missense_variant 2/7 ENST00000320954.11 NP_006362.1
CRTAPNM_001393363.1 linkuse as main transcriptc.534C>G p.Asp178Glu missense_variant 2/6 NP_001380292.1
CRTAPNM_001393364.1 linkuse as main transcriptc.534C>G p.Asp178Glu missense_variant 2/6 NP_001380293.1
CRTAPNM_001393365.1 linkuse as main transcriptc.472-4002C>G intron_variant NP_001380294.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAPENST00000320954.11 linkuse as main transcriptc.534C>G p.Asp178Glu missense_variant 2/71 NM_006371.5 ENSP00000323696 P1
CRTAPENST00000449224.1 linkuse as main transcriptc.534C>G p.Asp178Glu missense_variant 2/62 ENSP00000409997
CRTAPENST00000485310.1 linkuse as main transcriptn.128C>G non_coding_transcript_exon_variant 2/54

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 7 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Benign
1.4
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.85
T;T
M_CAP
Uncertain
0.086
D
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Uncertain
0.23
D
MutationAssessor
Pathogenic
3.1
M;.
MutationTaster
Benign
0.000016
P;P
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.5
N;N
REVEL
Uncertain
0.56
Sift
Benign
0.11
T;T
Sift4G
Benign
0.14
T;T
Polyphen
1.0
D;D
Vest4
0.71
MutPred
0.58
Loss of glycosylation at K174 (P = 0.0545);Loss of glycosylation at K174 (P = 0.0545);
MVP
0.71
MPC
0.40
ClinPred
0.87
D
GERP RS
-7.1
Varity_R
0.13
gMVP
0.61

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.

Other links and lift over

dbSNP: rs4076086; hg19: chr3-33161898; API