3-39333032-C-G

Variant summary

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

The NM_005201.4(CCR8):​c.701C>G​(p.Thr234Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 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: 6.8e-7 ( 0 hom. )

Consequence

CCR8
NM_005201.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.134
Variant links:
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]

Genome browser will be placed here

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=0.17338976).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCR8NM_005201.4 linkc.701C>G p.Thr234Ser missense_variant Exon 2 of 2 ENST00000326306.5 NP_005192.1 P51685-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCR8ENST00000326306.5 linkc.701C>G p.Thr234Ser missense_variant Exon 2 of 2 1 NM_005201.4 ENSP00000326432.4 P51685-1
CCR8ENST00000414803.1 linkc.*171C>G 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000390104.1 C9JIP9
ENSG00000287780ENST00000655387.1 linkn.370-40082G>C intron_variant Intron 3 of 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250726
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135478
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:
6.84e-7
AC:
1
AN:
1461770
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.701C>G (p.T234S) alteration is located in exon 2 (coding exon 1) of the CCR8 gene. This alteration results from a C to G substitution at nucleotide position 701, causing the threonine (T) at amino acid position 234 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.050
Eigen_PC
Benign
-0.030
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.75
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.18
Sift
Benign
0.14
T
Sift4G
Benign
0.60
T
Polyphen
0.83
P
Vest4
0.12
MutPred
0.45
Gain of disorder (P = 0.0354);
MVP
0.83
MPC
0.18
ClinPred
0.37
T
GERP RS
3.8
Varity_R
0.073
gMVP
0.094

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: rs1559379518; hg19: chr3-39374523; API