6-167136510-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031409.4(CCR6):c.280C>T(p.Leu94Phe) 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 pathogenic 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: 1.75

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR6	NM_031409.4	c.280C>T	p.Leu94Phe	missense_variant	3/3	ENST00000341935.10
CCR6	NM_001394582.1	c.280C>T	p.Leu94Phe	missense_variant	4/4
CCR6	NM_004367.6	c.280C>T	p.Leu94Phe	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR6	ENST00000341935.10	c.280C>T	p.Leu94Phe	missense_variant	3/3	1	NM_031409.4	P1
CCR6	ENST00000349984.6	c.280C>T	p.Leu94Phe	missense_variant	4/4	1		P1
CCR6	ENST00000400926.5	c.280C>T	p.Leu94Phe	missense_variant	3/3	2		P1
CCR6	ENST00000643861.1	c.280C>T	p.Leu94Phe	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Aug 03, 2022

The c.280C>T (p.L94F) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a C to T substitution at nucleotide position 280, causing the leucine (L) at amino acid position 94 to be replaced by a phenylalanine (F). 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	0.22
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D;T;.;.;.
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.73	T
Polyphen		0.98	.;D;D;D;D
Vest4		0.63, 0.62
MutPred		0.75		Loss of stability (P = 0.0972);Loss of stability (P = 0.0972);Loss of stability (P = 0.0972);Loss of stability (P = 0.0972);Loss of stability (P = 0.0972);
MVP		0.81
MPC		1.5
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.48
gMVP		0.50

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: rs1781852222; hg19: chr6-167549998;