Variant 10-97895952-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018058.7(CRTAC1):c.1250T>G(p.Met417Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CRTAC1
NM_018058.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

CRTAC1 (HGNC:14882): (cartilage acidic protein 1) This gene encodes a glycosylated extracellular matrix protein that is found in the interterritorial matrix of articular deep zone cartilage. This protein is used as a marker to distinguish chondrocytes from osteoblasts and mesenchymal stem cells in culture. The presence of FG-GAP motifs and an RGD integrin-binding motif suggests that this protein may be involved in cell-cell or cell-matrix interactions. Copy number alterations in this gene have been observed in neurofibromatosis type 1-associated glomus tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CRTAC1 links:

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ACMG classification

Classification made for transcript

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=0.17161551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAC1	NM_018058.7 linkuse as main transcript	c.1250T>G	p.Met417Arg	missense_variant	10/15	ENST00000370597.8	NP_060528.3	Q9NQ79-1
CRTAC1	NM_001206528.3 linkuse as main transcript	c.1250T>G	p.Met417Arg	missense_variant	10/15		NP_001193457.1	Q9NQ79-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRTAC1	ENST00000370597.8 linkuse as main transcript	c.1250T>G	p.Met417Arg	missense_variant	10/15	1	NM_018058.7	ENSP00000359629.3	Q9NQ79-1
CRTAC1	ENST00000309155.3 linkuse as main transcript	c.1226T>G	p.Met409Arg	missense_variant	9/14	1		ENSP00000310810.3	A0A0C4DFP6
CRTAC1	ENST00000370591.6 linkuse as main transcript	c.1250T>G	p.Met417Arg	missense_variant	10/15	5		ENSP00000359623.2	Q9NQ79-2
CRTAC1	ENST00000413387.5 linkuse as main transcript	c.938T>G	p.Met313Arg	missense_variant	8/12	2		ENSP00000408445.1	Q5T4F6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251392

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.1250T>G (p.M417R) alteration is located in exon 10 (coding exon 10) of the CRTAC1 gene. This alteration results from a T to G substitution at nucleotide position 1250, causing the methionine (M) at amino acid position 417 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0032

T;T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.092

Sift

Benign

0.57

T;T;T;T

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.36, 0.36, 0.36

MutPred

0.56

.;Gain of methylation at M417 (P = 0.0329);Gain of methylation at M417 (P = 0.0329);.;

MVP

0.24

MPC

0.51

ClinPred

0.28

GERP RS

5.2

Varity_R

0.51

gMVP

0.84

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over