rs139226823

Variant names:

• chrX-71616597-C-A
• rs139226823
• NM_001504.2:c.875G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-71616597-C-A
• chrX-71616597-C-G
• chrX-71616597-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001504.2(CXCR3):​c.875G>T​(p.Arg292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CXCR3 NM_001504.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

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=0.06897247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR3	NM_001504.2	c.875G>T	p.Arg292Leu	missense_variant	Exon 2 of 2	ENST00000373693.4	NP_001495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR3	ENST00000373693.4	c.875G>T	p.Arg292Leu	missense_variant	Exon 2 of 2	1	NM_001504.2	ENSP00000362797.3
CXCR3	ENST00000373691.4	c.1016G>T	p.Arg339Leu	missense_variant	Exon 2 of 2	1		ENSP00000362795.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.054
DANN	Benign	0.59
DEOGEN2	Benign	0.11	.;T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.54	.;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.034
Sift	Benign	0.45	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0070	B;B
Vest4		0.078
MutPred		0.42		.;Loss of methylation at R292 (P = 0.0111);
MVP		0.78
MPC		0.90
ClinPred		0.057	T
GERP RS		0.48
Varity_R		0.074
gMVP		0.54

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

Other links and lift over

dbSNP: rs139226823; hg19: chrX-70836447;