Genetic Variant CXCL3:p.Arg17Pro (chr4-74038562-C-G) – 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.50G>C(p.Arg17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,338,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R17L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CXCL3
NM_002090.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

0 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=0.16900656).

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.50G>C	p.Arg17Pro	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.50G>C	p.Arg17Pro	missense	Exon 1 of 4	ENSP00000296026.4	P19876
CXCL3	ENST00000511669.1	TSL:1	n.246G>C		non_coding_transcript_exon	Exon 1 of 2
CXCL3	ENST00000502974.1	TSL:2	n.128G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1338304

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

658948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26912

American (AMR)

AF:

0.00

AC:

AN:

27358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22958

East Asian (EAS)

AF:

0.00

AC:

AN:

28668

South Asian (SAS)

AF:

0.00

AC:

AN:

72122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4850

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1053688

Other (OTH)

AF:

0.00

AC:

AN:

55344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.11

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.57

M_CAP

Benign

0.034

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

PhyloP100

-0.31

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.70

REVEL

Benign

0.094

Sift

Benign

0.26

Sift4G

Benign

0.29

Polyphen

0.89

Vest4

0.12

MutPred

0.53

Loss of helix (P = 0.0017)

MVP

0.13

MPC

0.20

ClinPred

0.58

GERP RS

0.87

PromoterAI

0.18

Neutral

(source)

Varity_R

0.13

gMVP

0.18

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over