4-73998288-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002994.5(CXCL5):ā€‹c.160A>Gā€‹(p.Thr54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000013 ( 0 hom. )

Consequence

CXCL5
NM_002994.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.687
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12195334).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CXCL5NM_002994.5 linkuse as main transcriptc.160A>G p.Thr54Ala missense_variant 2/4 ENST00000296027.5 NP_002985.1 P42830Q6I9S7
LOC124900715XR_007058140.1 linkuse as main transcriptn.61T>C non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CXCL5ENST00000296027.5 linkuse as main transcriptc.160A>G p.Thr54Ala missense_variant 2/41 NM_002994.5 ENSP00000296027.4 P42830
ENSG00000287037ENST00000669992.1 linkuse as main transcriptn.356T>C non_coding_transcript_exon_variant 1/3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461884
Hom.:
0
Cov.:
34
AF XY:
0.0000179
AC XY:
13
AN XY:
727244
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:
0.0000162
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 03, 2024The c.160A>G (p.T54A) alteration is located in exon 2 (coding exon 2) of the CXCL5 gene. This alteration results from a A to G substitution at nucleotide position 160, causing the threonine (T) at amino acid position 54 to be replaced by an alanine (A). 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
0.14
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
1.7
DANN
Benign
0.78
DEOGEN2
Benign
0.26
T
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Pathogenic
2.9
M
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.077
Sift
Uncertain
0.015
D
Sift4G
Benign
0.11
T
Polyphen
0.17
B
Vest4
0.10
MutPred
0.61
Loss of sheet (P = 0.0817);
MVP
0.10
MPC
0.14
ClinPred
0.20
T
GERP RS
-5.0
Varity_R
0.11
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: chr4-74864005; API