6-167137077-A-G

Variant summary

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

The NM_031409.4(CCR6):c.847A>G(p.Lys283Glu) 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 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • 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: -0.272

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=0.076789916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR6	NM_031409.4	c.847A>G	p.Lys283Glu	missense_variant	3/3	ENST00000341935.10
CCR6	NM_001394582.1	c.847A>G	p.Lys283Glu	missense_variant	4/4
CCR6	NM_004367.6	c.847A>G	p.Lys283Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR6	ENST00000341935.10	c.847A>G	p.Lys283Glu	missense_variant	3/3	1	NM_031409.4	P1
CCR6	ENST00000349984.6	c.847A>G	p.Lys283Glu	missense_variant	4/4	1		P1
CCR6	ENST00000400926.5	c.847A>G	p.Lys283Glu	missense_variant	3/3	2		P1
CCR6	ENST00000643861.1	c.847A>G	p.Lys283Glu	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

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: 0.0000166

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 24, 2023

The c.847A>G (p.K283E) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a A to G substitution at nucleotide position 847, causing the lysine (K) at amino acid position 283 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	1.9
Dann	Benign	0.34
DEOGEN2	Benign	0.069	T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.54	T;.;.;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.42	N;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.43	T;.;T;T
Sift4G	Benign	0.73	T;.;T;T
Polyphen		0.0020	B;B;B;B
Vest4		0.062
MutPred		0.52		Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);
MVP		0.57
MPC		0.82
ClinPred		0.073	T
GERP RS		-1.4
Varity_R		0.12
gMVP		0.31

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: chr6-167550565;