Variant 17-34357535-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005408.3(CCL13):c.137A>G(p.Gln46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.000011 ( 0 hom. )

Consequence

CCL13
NM_005408.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120

Variant links:

Genes affected

CCL13 (HGNC:10611): (C-C motif chemokine ligand 13) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. This chemokine plays a role in accumulation of leukocytes during inflammation. It may also be involved in the recruitment of monocytes into the arterial wall during artherosclerosis. [provided by RefSeq, Sep 2014]

CCL13 links:

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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=0.18035233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL13	NM_005408.3 linkuse as main transcript	c.137A>G	p.Gln46Arg	missense_variant	2/3	ENST00000225844.7	NP_005399.1	Q99616

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL13	ENST00000225844.7 linkuse as main transcript	c.137A>G	p.Gln46Arg	missense_variant	2/3	1	NM_005408.3	ENSP00000225844.2		Q99616
CCL13	ENST00000577681.1 linkuse as main transcript	c.50A>G	p.Gln17Arg	missense_variant	1/2	1		ENSP00000463667.1		J3QLQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251272

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135786

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461330

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726892

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2023

The c.137A>G (p.Q46R) alteration is located in exon 2 (coding exon 2) of the CCL13 gene. This alteration results from a A to G substitution at nucleotide position 137, causing the glutamine (Q) at amino acid position 46 to be replaced by an arginine (R). 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

0.093

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.2

DANN

Benign

0.70

DEOGEN2

Benign

0.087

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.54

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.11

Sift

Benign

0.22

Sift4G

Benign

0.41

Polyphen

0.011

Vest4

0.20

MutPred

0.42

Gain of MoRF binding (P = 0.0198);

MVP

0.27

MPC

0.13

ClinPred

0.099

GERP RS

4.6

Varity_R

0.37

gMVP

0.095

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over