rs766079896

Variant summary

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

The NM_001504.2(CXCR3):ā€‹c.925A>Gā€‹(p.Met309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,126 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)
Exomes š‘“: 0.0000018 ( 0 hom. 0 hem. )

Consequence

CXCR3
NM_001504.2 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27
Variant links:
Genes affected
CXCR3 (HGNC:4540): (C-X-C motif chemokine receptor 3) This gene encodes a G protein-coupled receptor with selectivity for three chemokines, termed CXCL9/Mig (monokine induced by interferon-g), CXCL10/IP10 (interferon-g-inducible 10 kDa protein) and CXCL11/I-TAC (interferon-inducible T cell a-chemoattractant). Binding of chemokines to this protein induces cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the isoforms (CXCR3-B) shows high affinity binding to chemokine, CXCL4/PF4 (PMID:12782716). [provided by RefSeq, Jun 2011]

Genome browser will be placed here

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=0.098959416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CXCR3NM_001504.2 linkc.925A>G p.Met309Val missense_variant Exon 2 of 2 ENST00000373693.4 NP_001495.1 P49682-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CXCR3ENST00000373693.4 linkc.925A>G p.Met309Val missense_variant Exon 2 of 2 1 NM_001504.2 ENSP00000362797.3 P49682-1
CXCR3ENST00000373691.4 linkc.1066A>G p.Met356Val missense_variant Exon 2 of 2 1 ENSP00000362795.4 P49682-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000110
AC:
2
AN:
181924
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66524
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:
0.0000246
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1097126
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
362564
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:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.2
DANN
Benign
0.90
DEOGEN2
Benign
0.13
.;T
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.099
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.93
.;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.53
N;N
REVEL
Benign
0.052
Sift
Benign
0.71
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.0090
B;B
Vest4
0.14
MutPred
0.40
.;Loss of catalytic residue at M309 (P = 0.0871);
MVP
0.86
MPC
0.74
ClinPred
0.049
T
GERP RS
2.7
Varity_R
0.061
gMVP
0.41

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.

Other links and lift over

dbSNP: rs766079896; hg19: chrX-70836397; API