rs199927524

Variant names:

• chrX-71616834-G-A
• rs199927524
• NM_001504.2:c.638C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001504.2(CXCR3):​c.638C>T​(p.Thr213Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,208,545 control chromosomes in the GnomAD database, including 1 homozygotes. There are 59 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00017 (1 hom. 57 hem.)
• Consequence: CXCR3 NM_001504.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.213
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13830847).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001504.2. 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
	CXCR3	NM_001504.2	MANE Select	c.638C>T	p.Thr213Met	missense	Exon 2 of 2	NP_001495.1	P49682-1
	CXCR3	NM_001142797.2		c.779C>T	p.Thr260Met	missense	Exon 2 of 2	NP_001136269.1	P49682-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR3	ENST00000373693.4	TSL:1 MANE Select	c.638C>T	p.Thr213Met	missense	Exon 2 of 2	ENSP00000362797.3	P49682-1
	CXCR3	ENST00000373691.4	TSL:1	c.779C>T	p.Thr260Met	missense	Exon 2 of 2	ENSP00000362795.4	P49682-2

Frequencies

GnomAD3 genomes AF: 0.0000889 AC: 10 AN: 112513 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000754 AC: 13 AN: 172467 AF XY: 0.0000833

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 189 AN: 1096032 Hom.: 1 Cov.: 32 AF XY: 0.000158 AC XY: 57 AN XY: 361770

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.0000573 AC: 2 AN: 34917

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19298

East Asian (EAS) AF: 0.00 AC: 0 AN: 30137

South Asian (SAS) AF: 0.00 AC: 0 AN: 53666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.000216 AC: 182 AN: 841383

Other (OTH) AF: 0.000109 AC: 5 AN: 46008

GnomAD4 genome AF: 0.0000889 AC: 10 AN: 112513 Hom.: 0 Cov.: 23 AF XY: 0.0000577 AC XY: 2 AN XY: 34669

African (AFR) AF: 0.00 AC: 0 AN: 31044

American (AMR) AF: 0.00 AC: 0 AN: 10708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2705

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6209

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53207

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.000223 Hom.: 11

Bravo AF: 0.0000793

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.21
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.29	T
Polyphen		0.82	P
Vest4		0.14
MVP		0.96
MPC		0.91
ClinPred		0.056	T
GERP RS		1.1
Varity_R		0.034
gMVP		0.39
Mutation Taster		=99/1	polymorphism

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: rs199927524; hg19: chrX-70836684; COSMIC: COSV107485308; COSMIC: COSV107485308;