10-97882797-C-T

Variant names:

• chr10-97882797-C-T
• rs1390128854
• NM_018058.7:c.1664G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018058.7(CRTAC1):​c.1664G>A​(p.Gly555Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G555V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CRTAC1 NM_018058.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018058.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	NM_018058.7	MANE Select	c.1664G>A	p.Gly555Asp	missense	Exon 13 of 15	NP_060528.3
	CRTAC1	NM_001206528.3		c.1664G>A	p.Gly555Asp	missense	Exon 13 of 15	NP_001193457.1	Q9NQ79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	ENST00000370597.8	TSL:1 MANE Select	c.1664G>A	p.Gly555Asp	missense	Exon 13 of 15	ENSP00000359629.3	Q9NQ79-1
	CRTAC1	ENST00000309155.4	TSL:1	c.1640G>A	p.Gly547Asp	missense	Exon 13 of 15	ENSP00000310810.3
	CRTAC1	ENST00000856696.1		c.1709G>A	p.Gly570Asp	missense	Exon 14 of 16	ENSP00000526755.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.8	N
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.42		Gain of disorder (P = 0.0994)
MVP		0.96
MPC		1.1
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.75
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1390128854; hg19: chr10-99642554;