9-34709509-C-A

Variant summary

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

The NM_002989.4(CCL21):c.362G>T(p.Gly121Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000041 ( 0 hom. )

Consequence

CCL21
NM_002989.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.823

Variant links:

Genes affected

CCL21 (HGNC:10620): (C-C motif chemokine ligand 21) This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by this gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19). [provided by RefSeq, Sep 2014]

CCL21 links:

(HGNC:):

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=0.23555398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCL21	NM_002989.4 linkuse as main transcript	c.362G>T	p.Gly121Val	missense_variant	3/4	ENST00000259607.7
PHF24	XM_047423102.1 linkuse as main transcript	c.133+6471C>A		intron_variant
PHF24	XM_047423103.1 linkuse as main transcript	c.70+6471C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCL21	ENST00000259607.7 linkuse as main transcript	c.362G>T	p.Gly121Val	missense_variant	3/4	1	NM_002989.4	P1
	ENST00000664167.1 linkuse as main transcript	n.86+6471C>A		intron_variant, non_coding_transcript_variant
CCL21	ENST00000378792.1 linkuse as main transcript	c.362G>T	p.Gly121Val	missense_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251136

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00000410

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

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

Dec 09, 2023

The c.362G>T (p.G121V) alteration is located in exon 3 (coding exon 3) of the CCL21 gene. This alteration results from a G to T substitution at nucleotide position 362, causing the glycine (G) at amino acid position 121 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

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.061

Sift

Uncertain

0.0080

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.94

P;.

Vest4

0.36

MutPred

0.26

Loss of glycosylation at K120 (P = 0.098);Loss of glycosylation at K120 (P = 0.098);

MVP

0.53

MPC

0.36

ClinPred

0.41

GERP RS

3.2

Varity_R

0.11

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

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