rs1040366227

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018058.7(CRTAC1):​c.1544G>C​(p.Arg515Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R515Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

CRTAC1
NM_018058.7 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRTAC1NM_018058.7 linkc.1544G>C p.Arg515Pro missense_variant Exon 12 of 15 ENST00000370597.8 NP_060528.3 Q9NQ79-1
CRTAC1NM_001206528.3 linkc.1544G>C p.Arg515Pro missense_variant Exon 12 of 15 NP_001193457.1 Q9NQ79-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRTAC1ENST00000370597.8 linkc.1544G>C p.Arg515Pro missense_variant Exon 12 of 15 1 NM_018058.7 ENSP00000359629.3 Q9NQ79-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.13e-7
AC:
1
AN:
1402508
Hom.:
0
Cov.:
31
AF XY:
0.00000144
AC XY:
1
AN XY:
692154
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000277
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;D;.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Pathogenic
0.31
D
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Uncertain
0.12
D
MutationAssessor
Pathogenic
3.2
.;M;M;.
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0050
D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.87, 0.86, 0.86
MutPred
0.70
.;Gain of glycosylation at S519 (P = 0.0685);Gain of glycosylation at S519 (P = 0.0685);.;
MVP
0.80
MPC
1.2
ClinPred
0.99
D
GERP RS
3.7
Varity_R
0.62
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr10-99644051; API