6-167136432-G-A

Variant names:

• chr6-167136432-G-A
• NM_031409.4:c.202G>A

Variant summary

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

The NM_031409.4(CCR6):​c.202G>A​(p.Val68Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24
• Publications: 0 publications found

Genes affected

CCR6 (HGNC:1607): (C-C motif chemokine receptor 6) 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. The gene is preferentially expressed by immature dendritic cells and memory T cells. The ligand of this receptor is macrophage inflammatory protein 3 alpha (MIP-3 alpha). This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dentritic and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000272980 (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_031409.4. 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
	CCR6	NM_031409.4	MANE Select	c.202G>A	p.Val68Met	missense	Exon 3 of 3	NP_113597.2
	CCR6	NM_001394582.1		c.202G>A	p.Val68Met	missense	Exon 4 of 4	NP_001381511.1	P51684
	CCR6	NM_004367.6		c.202G>A	p.Val68Met	missense	Exon 3 of 3	NP_004358.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR6	ENST00000341935.10	TSL:1 MANE Select	c.202G>A	p.Val68Met	missense	Exon 3 of 3	ENSP00000343952.5	P51684
	CCR6	ENST00000349984.6	TSL:1	c.202G>A	p.Val68Met	missense	Exon 4 of 4	ENSP00000339393.4	P51684
	ENSG00000272980	ENST00000705249.1		c.*155G>A		3_prime_UTR	Exon 13 of 13	ENSP00000516101.1	A0A994J5H4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459926 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726152

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111294

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.29	T
Polyphen		0.93	P
Vest4		0.36
MutPred		0.51		Loss of catalytic residue at V68 (P = 0.0077)
MVP		0.79
MPC		1.4
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.30
gMVP		0.26
Mutation Taster		=62/38	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

hg19: chr6-167549920;