16-57358823-C-T

Variant names:

• chr16-57358823-C-T
• rs1321086437
• NM_002990.5:c.7C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002990.5(CCL22):​c.7C>T​(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CCL22 NM_002990.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24796578).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002990.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	NM_002990.5	MANE Select	c.7C>T	p.Arg3Cys	missense	Exon 1 of 3	NP_002981.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	ENST00000219235.5	TSL:1 MANE Select	c.7C>T	p.Arg3Cys	missense	Exon 1 of 3	ENSP00000219235.4
	CCL22	ENST00000941195.1		c.7C>T	p.Arg3Cys	missense	Exon 2 of 4	ENSP00000611254.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251432 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460574 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726662

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86238

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110908

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.20
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.070
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.046	D
Polyphen		0.96	D
Vest4		0.19
MutPred		0.42		Gain of catalytic residue at M1 (P = 0.0053)
MVP		0.28
MPC		0.44
ClinPred		0.80	D
GERP RS		0.011
PromoterAI		-0.052	Neutral
Varity_R		0.068
gMVP		0.64
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1321086437; hg19: chr16-57392735; COSMIC: COSV54660478;