chr3-33114090-C-T

Variant names:

• chr3-33114090-C-T
• rs758652009
• NM_006371.5:c.13C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006371.5(CRTAP):​c.13C>T​(p.Arg5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,309,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CRTAP NM_006371.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10839626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAP	NM_006371.5	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 7	ENST00000320954.11	NP_006362.1
CRTAP	NM_001393363.1	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 6		NP_001380292.1
CRTAP	NM_001393364.1	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 6		NP_001380293.1
CRTAP	NM_001393365.1	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 6		NP_001380294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAP	ENST00000320954.11	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 7	1	NM_006371.5	ENSP00000323696.5
CRTAP	ENST00000449224.1	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 6	2		ENSP00000409997.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000145 AC: 19 AN: 1309076 Hom.: 0 Cov.: 31 AF XY: 0.0000108 AC XY: 7 AN XY: 646254

Gnomad4 AFR exome AF: 0.0000381

Gnomad4 AMR exome AF: 0.00

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: 0.0000172

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.067
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.090	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.44		Loss of glycosylation at R3 (P = 0.0312);Loss of glycosylation at R3 (P = 0.0312);
MVP		0.33
MPC		0.16
ClinPred		0.23	T
GERP RS		0.59
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.0
Varity_R		0.15
gMVP		0.58

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

Other links and lift over

dbSNP: rs758652009; hg19: chr3-33155582;