NM_002990.5:c.142C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002990.5(CCL22):​c.142C>A​(p.Arg48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 𝑓: 0.000012 ( 0 hom. )

Consequence

CCL22
NM_002990.5 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.281
Variant links:
Genes affected
CCL22 (HGNC:10621): (C-C motif chemokine ligand 22) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. 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, dendritic cells, natural killer cells and for chronically activated T lymphocytes. It also displays a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. The product of this gene binds to chemokine receptor CCR4. This chemokine may play a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. [provided by RefSeq, Sep 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37548864).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCL22NM_002990.5 linkc.142C>A p.Arg48Ser missense_variant Exon 2 of 3 ENST00000219235.5 NP_002981.2 O00626
CCL22XM_047434449.1 linkc.181C>A p.Arg61Ser missense_variant Exon 3 of 4 XP_047290405.1
CCL22XM_047434450.1 linkc.142C>A p.Arg48Ser missense_variant Exon 3 of 4 XP_047290406.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCL22ENST00000219235.5 linkc.142C>A p.Arg48Ser missense_variant Exon 2 of 3 1 NM_002990.5 ENSP00000219235.4 O00626

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251464
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135910
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461856
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727232
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:
0.0000153
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.085
Sift
Uncertain
0.018
D
Sift4G
Uncertain
0.030
D
Polyphen
0.90
P
Vest4
0.47
MutPred
0.45
Loss of MoRF binding (P = 0.0114);
MVP
0.16
MPC
0.79
ClinPred
0.88
D
GERP RS
2.1
Varity_R
0.18
gMVP
0.74

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.

Other links and lift over

dbSNP: rs145382097; hg19: chr16-57394417; COSMIC: COSV54660800; API