NM_005201.4:c.730G>A

Variant names:

• chr3-39333061-G-A
• rs965136311
• NM_005201.4:c.730G>A

Variant summary

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

The NM_005201.4(CCR8):​c.730G>A​(p.Val244Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V244F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR8 NM_005201.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.97
• Publications: 0 publications found

Genes affected

CCR8 (HGNC:1609): (C-C motif chemokine receptor 8) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptors are important for the migration of various cell types into the inflammatory sites. This receptor protein preferentially expresses in the thymus. I-309, thymus activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta) have been identified as ligands of this receptor. Studies of this receptor and its ligands suggested its role in regulation of monocyte chemotaxis and thymic cell apoptosis. More specifically, this receptor may contribute to the proper positioning of activated T cells within the antigenic challenge sites and specialized areas of lymphoid tissues. This gene is located at the chemokine receptor gene cluster region. [provided by RefSeq, Jul 2008]

ENSG00000287780 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005201.4. 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
	CCR8	NM_005201.4	MANE Select	c.730G>A	p.Val244Ile	missense	Exon 2 of 2	NP_005192.1	P51685-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR8	ENST00000326306.5	TSL:1 MANE Select	c.730G>A	p.Val244Ile	missense	Exon 2 of 2	ENSP00000326432.4	P51685-1
	CCR8	ENST00000414803.2	TSL:1	c.*200G>A		3_prime_UTR	Exon 3 of 3	ENSP00000390104.1	C9JIP9
	ENSG00000287780	ENST00000655387.2		n.435-40111C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.37	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.046	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.54		Loss of catalytic residue at V244 (P = 0.0626)
MVP		0.85
MPC		0.48
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.13
Mutation Taster		=82/18	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: rs965136311; hg19: chr3-39374552;