X-71616993-T-G

Position:

• chrX-71616993-T-G

Variant summary

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

The ENST00000373693.4(CXCR3):​c.479A>C​(p.Tyr160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CXCR3 ENST00000373693.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.786

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2	c.479A>C	p.Tyr160Ser	missense_variant	2/2	ENST00000373693.4	NP_001495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR3	ENST00000373693.4	c.479A>C	p.Tyr160Ser	missense_variant	2/2	1	NM_001504.2	ENSP00000362797	P1
CXCR3	ENST00000373691.4	c.620A>C	p.Tyr207Ser	missense_variant	2/2	1		ENSP00000362795

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.620A>C (p.Y207S) alteration is located in exon 2 (coding exon 1) of the CXCR3 gene. This alteration results from a A to C substitution at nucleotide position 620, causing the tyrosine (Y) at amino acid position 207 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	.;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.71	.;N
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.49
Sift	Benign	0.063	T;D
Sift4G	Benign	0.16	T;T
Polyphen		0.45	B;P
Vest4		0.45
MutPred		0.63		.;Gain of disorder (P = 0.0023);
MVP		0.95
MPC		2.1
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.89
gMVP		0.82

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: chrX-70836843;