10-97865567-C-T

Variant names:

• chr10-97865567-C-T
• NM_018058.7:c.1967G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018058.7(CRTAC1):​c.1967G>A​(p.Ser656Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S656T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CRTAC1 NM_018058.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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]

GOLGA7B (HGNC:31668): (golgin A7 family member B) Enables enzyme binding activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be located in Golgi membrane. Predicted to be part of palmitoyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03227997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAC1	NM_018058.7	c.1967G>A	p.Ser656Asn	missense_variant	Exon 15 of 15	ENST00000370597.8	NP_060528.3
GOLGA7B	NM_001010917.3	c.394-23C>T		intron_variant	Intron 4 of 4	ENST00000370602.6	NP_001010917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAC1	ENST00000370597.8	c.1967G>A	p.Ser656Asn	missense_variant	Exon 15 of 15	1	NM_018058.7	ENSP00000359629.3
GOLGA7B	ENST00000370602.6	c.394-23C>T		intron_variant	Intron 4 of 4	1	NM_001010917.3	ENSP00000359634.1
CRTAC1	ENST00000413387	c.*37G>A		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000408445.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457788 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724406

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.6
DANN	Benign	0.89
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.19
Sift	Benign	0.35	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.041
MutPred		0.11		Loss of glycosylation at S656 (P = 0.0778);
MVP		0.25
MPC		0.43
ClinPred		0.26	T
GERP RS		-0.074
Varity_R		0.046
gMVP		0.35

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: chr10-99625324;