chr10-97895961-C-T

Position:

• chr10-97895961-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018058.7(CRTAC1):​c.1241G>A​(p.Gly414Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRTAC1 NM_018058.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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]

ACMG classification

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, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAC1	NM_018058.7	c.1241G>A	p.Gly414Glu	missense_variant	10/15	ENST00000370597.8	NP_060528.3
CRTAC1	NM_001206528.3	c.1241G>A	p.Gly414Glu	missense_variant	10/15		NP_001193457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAC1	ENST00000370597.8	c.1241G>A	p.Gly414Glu	missense_variant	10/15	1	NM_018058.7	ENSP00000359629.3
CRTAC1	ENST00000309155.3	c.1217G>A	p.Gly406Glu	missense_variant	9/14	1		ENSP00000310810.3
CRTAC1	ENST00000370591.6	c.1241G>A	p.Gly414Glu	missense_variant	10/15	5		ENSP00000359623.2
CRTAC1	ENST00000413387.5	c.929G>A	p.Gly310Glu	missense_variant	8/12	2		ENSP00000408445.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.1241G>A (p.G414E) alteration is located in exon 10 (coding exon 10) of the CRTAC1 gene. This alteration results from a G to A substitution at nucleotide position 1241, causing the glycine (G) at amino acid position 414 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;D;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.4	.;M;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.9	D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.74, 0.73, 0.73
MutPred		0.59		.;Gain of disorder (P = 0.13);Gain of disorder (P = 0.13);.;
MVP		0.64
MPC		1.1
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.49
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-99655718; COSMIC: COSV100084907;