Genetic Variant CXCL3:p.Ala2Gly (chr4-74038607-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002090.3(CXCL3):c.5C>G(p.Ala2Gly) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCL3
NM_002090.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

Publications

6 publications found

Variant links:

Genes affected

CXCL3 (HGNC:4604): (C-X-C motif chemokine ligand 3) This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils. [provided by RefSeq, Sep 2014]

CXCL3 links:

ENSG00000287037 (HGNC:58815):

ENSG00000287037 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21351135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002090.3. 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
	CXCL3	NM_002090.3	MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	NP_002081.2	P19876

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CXCL3	ENST00000296026.4	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	ENSP00000296026.4	P19876
CXCL3	ENST00000511669.1	TSL:1	n.201C>G		non_coding_transcript_exon	Exon 1 of 2
CXCL3	ENST00000502974.1	TSL:2	n.83C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

73802

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1319398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

649276

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.00

AC:

AN:

24634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22042

East Asian (EAS)

AF:

0.00

AC:

AN:

28554

South Asian (SAS)

AF:

0.00

AC:

AN:

69752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4530

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047724

Other (OTH)

AF:

0.00

AC:

AN:

54714

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

Eigen

Benign

0.046

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.26

M_CAP

Benign

0.036

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.60

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.78

REVEL

Benign

0.074

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.058

Polyphen

0.99

Vest4

0.14

MutPred

0.17

Loss of stability (P = 0.0323)

MVP

0.19

MPC

0.30

ClinPred

0.60

GERP RS

0.061

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.075

gMVP

0.079

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over