chr6-167137023-G-A

Position:

• chr6-167137023-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031409.4(CCR6):​c.793G>A​(p.Ala265Thr) 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. 13/21 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: 1.13

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]

ACMG classification

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=0.21451658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4	c.793G>A	p.Ala265Thr	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1	c.793G>A	p.Ala265Thr	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6	c.793G>A	p.Ala265Thr	missense_variant	3/3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10	c.793G>A	p.Ala265Thr	missense_variant	3/3	1	NM_031409.4	ENSP00000343952	P1
CCR6	ENST00000349984.6	c.793G>A	p.Ala265Thr	missense_variant	4/4	1		ENSP00000339393	P1
CCR6	ENST00000400926.5	c.793G>A	p.Ala265Thr	missense_variant	3/3	2		ENSP00000383715	P1
CCR6	ENST00000643861.1	c.793G>A	p.Ala265Thr	missense_variant	4/4			ENSP00000493637	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

May 13, 2024

The c.793G>A (p.A265T) 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 793, causing the alanine (A) at amino acid position 265 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	T;.;.;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	0.71	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.63	N;.;N;N
REVEL	Benign	0.030
Sift	Benign	0.058	T;.;T;T
Sift4G	Uncertain	0.047	D;.;D;D
Polyphen		0.11	B;B;B;B
Vest4		0.063
MutPred		0.43		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.51
MPC		0.61
ClinPred		0.33	T
GERP RS		3.0
Varity_R		0.090
gMVP		0.29

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

Other links and lift over

dbSNP: rs932769638; hg19: chr6-167550511;