NM_001371558.1:c.55C>T

Variant summary

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

The NM_001371558.1(CXCL13):​c.55C>T​(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,601,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CXCL13
NM_001371558.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779
Variant links:
Genes affected
CXCL13 (HGNC:10639): (C-X-C motif chemokine ligand 13) B lymphocyte chemoattractant, independently cloned and named Angie, is an antimicrobial peptide and CXC chemokine strongly expressed in the follicles of the spleen, lymph nodes, and Peyer's patches. It preferentially promotes the migration of B lymphocytes (compared to T cells and macrophages), apparently by stimulating calcium influx into, and chemotaxis of, cells expressing Burkitt's lymphoma receptor 1 (BLR-1). It may therefore function in the homing of B lymphocytes to follicles. [provided by RefSeq, Oct 2014]

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=0.16865277).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CXCL13NM_001371558.1 linkc.55C>T p.Pro19Ser missense_variant Exon 1 of 4 ENST00000682537.1 NP_001358487.1
CXCL13NM_006419.3 linkc.55C>T p.Pro19Ser missense_variant Exon 2 of 5 NP_006410.1 O43927Q53X90

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CXCL13ENST00000682537.1 linkc.55C>T p.Pro19Ser missense_variant Exon 1 of 4 NM_001371558.1 ENSP00000507688.1 O43927
CXCL13ENST00000286758.4 linkc.55C>T p.Pro19Ser missense_variant Exon 2 of 5 1 ENSP00000286758.4 O43927
CXCL13ENST00000506590.1 linkn.89C>T non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152160
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249022
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134574
show subpopulations
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 SAS exome
AF:
0.000134
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1448856
Hom.:
0
Cov.:
27
AF XY:
0.0000194
AC XY:
14
AN XY:
720464
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:
0.000190
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152278
Hom.:
1
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.55C>T (p.P19S) alteration is located in exon 2 (coding exon 1) of the CXCL13 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a serine (S). 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
0.17
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.064
Sift
Benign
0.25
T
Sift4G
Benign
0.096
T
Polyphen
0.98
D
Vest4
0.25
MutPred
0.43
Loss of loop (P = 0.0389);
MVP
0.35
MPC
0.69
ClinPred
0.91
D
GERP RS
2.1
Varity_R
0.032
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs767463762; hg19: chr4-78527074; API