6-167136876-G-A

Position:

• chr6-167136876-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031409.4(CCR6):​c.646G>A​(p.Gly216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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

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=0.35700575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4	c.646G>A	p.Gly216Arg	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1	c.646G>A	p.Gly216Arg	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6	c.646G>A	p.Gly216Arg	missense_variant	3/3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10	c.646G>A	p.Gly216Arg	missense_variant	3/3	1	NM_031409.4	ENSP00000343952.5
ENSG00000272980	ENST00000705249.1	c.*599G>A		3_prime_UTR_variant	13/13			ENSP00000516101.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.646G>A (p.G216R) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the glycine (G) at amino acid position 216 to be replaced by an arginine (R). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T;T;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T;.;.;.
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;.;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.23	T;.;T;T
Sift4G	Benign	0.38	T;.;T;T
Polyphen		0.45	B;B;B;B
Vest4		0.43
MutPred		0.75		Gain of methylation at G216 (P = 0.012);Gain of methylation at G216 (P = 0.012);Gain of methylation at G216 (P = 0.012);Gain of methylation at G216 (P = 0.012);
MVP		0.83
MPC		1.2
ClinPred		0.81	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-167550364;