Genetic Variant NM_002994.5:c.287C>T (chr4-73998051-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002994.5(CXCL5):c.287C>T(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CXCL5
NM_002994.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

CXCL5 (HGNC:10642): (C-X-C motif chemokine ligand 5) This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion. [provided by RefSeq, May 2013]

CXCL5 links:

ENSG00000287037 (HGNC:):

ENSG00000287037 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3363847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL5	NM_002994.5 link	c.287C>T	p.Ala96Val	missense_variant	Exon 3 of 4	ENST00000296027.5	NP_002985.1	P42830Q6I9S7
LOC124900715	XR_007058140.1 link	n.-177G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL5	ENST00000296027.5 link	c.287C>T	p.Ala96Val	missense_variant	Exon 3 of 4	1	NM_002994.5	ENSP00000296027.4		P42830
ENSG00000287037	ENST00000669992.1 link	n.119G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.287C>T (p.A96V) alteration is located in exon 3 (coding exon 3) of the CXCL5 gene. This alteration results from a C to T substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.81

M_CAP

Benign

0.0025

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.11

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0070

Polyphen

0.95

Vest4

0.41

MutPred

0.56

Loss of glycosylation at K100 (P = 0.1748);

MVP

0.39

MPC

0.23

ClinPred

0.98

GERP RS

3.8

Varity_R

0.45

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over