Variant 17-34357475-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.77A>G(p.Asp26Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,600,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCL13
NM_005408.3 missense, splice_region

Scores

Splicing: ADA: 0.00002427

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

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=0.12354034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL13	NM_005408.3 linkuse as main transcript	c.77A>G	p.Asp26Gly	missense_variant, splice_region_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.77A>G	p.Asp26Gly	missense_variant, splice_region_variant	2/3	1	NM_005408.3	ENSP00000225844.2		Q99616
CCL13	ENST00000577681.1 linkuse as main transcript	c.-11A>G		upstream_gene_variant		1		ENSP00000463667.1		J3QLQ9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250706

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448398

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

May 06, 2024

The c.77A>G (p.D26G) 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 77, causing the aspartic acid (D) at amino acid position 26 to be replaced by a glycine (G). 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

0.090

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.8

DANN

Benign

0.85

DEOGEN2

Benign

0.32

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.66

M_CAP

Benign

0.0092

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.034

Sift

Benign

0.16

Sift4G

Benign

0.31

Polyphen

0.033

Vest4

0.20

MutPred

0.54

Gain of catalytic residue at D26 (P = 0.1495);

MVP

0.35

MPC

0.14

ClinPred

0.046

GERP RS

1.9

Varity_R

0.33

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0

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

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