6-167137081-T-C

Variant names:

• chr6-167137081-T-C
• rs780682548
• NM_031409.4:c.851T>C

Variant summary

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

The NM_031409.4(CCR6):​c.851T>C​(p.Met284Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 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: 0.0000014 (0 hom.)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0210

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12517807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR6	NM_031409.4	c.851T>C	p.Met284Thr	missense_variant	Exon 3 of 3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1	c.851T>C	p.Met284Thr	missense_variant	Exon 4 of 4		NP_001381511.1
CCR6	NM_004367.6	c.851T>C	p.Met284Thr	missense_variant	Exon 3 of 3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10	c.851T>C	p.Met284Thr	missense_variant	Exon 3 of 3	1	NM_031409.4	ENSP00000343952.5
ENSG00000272980	ENST00000705249.1	c.*804T>C		3_prime_UTR_variant	Exon 13 of 13			ENSP00000516101.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 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: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.851T>C (p.M284T) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a T to C substitution at nucleotide position 851, causing the methionine (M) at amino acid position 284 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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.36
DANN	Benign	0.17
DEOGEN2	Benign	0.051	T;T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.46	T;.;.;.
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.010	N;.;N;N
REVEL	Benign	0.076
Sift	Benign	0.55	T;.;T;T
Sift4G	Benign	0.56	T;.;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.025
MutPred		0.65		Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);
MVP		0.23
MPC		0.68
ClinPred		0.032	T
GERP RS		-2.2
Varity_R		0.074
gMVP		0.46

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: rs780682548; hg19: chr6-167550569;