chr4-76022721-G-A

Variant names:

• chr4-76022721-G-A
• NM_001565.4:c.158C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001565.4(CXCL10):​c.158C>T​(p.Ala53Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CXCL10 NM_001565.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

Genes affected

CXCL10 (HGNC:10637): (C-X-C motif chemokine ligand 10) This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the 'cytokine storm' immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020]

ART3 (HGNC:725): (ADP-ribosyltransferase 3 (inactive)) This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001565.4. 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
	CXCL10	NM_001565.4	MANE Select	c.158C>T	p.Ala53Val	missense	Exon 2 of 4	NP_001556.2	P02778
	ART3	NM_001130017.3		c.-10+11401G>A		intron	N/A	NP_001123489.1	Q13508-2
	ART3	NM_001377177.1		c.-10+11401G>A		intron	N/A	NP_001364106.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL10	ENST00000306602.3	TSL:1 MANE Select	c.158C>T	p.Ala53Val	missense	Exon 2 of 4	ENSP00000305651.1	P02778
	ART3	ENST00000341029.9	TSL:1	c.-10+11401G>A		intron	N/A	ENSP00000343843.5	Q13508-2
	ART3	ENST00000513122.5	TSL:1	c.-125+11401G>A		intron	N/A	ENSP00000422287.1	E7ESB3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.073
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.076
Sift	Benign	0.052	T
Sift4G	Benign	0.084	T
Polyphen		0.86	P
Vest4		0.29
MutPred		0.48		Loss of disorder (P = 0.1238)
MVP		0.39
MPC		0.16
ClinPred		0.52	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.68
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-76943874;