6-167137047-G-T

Position:

• chr6-167137047-G-T

Variant summary

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

The NM_031409.4(CCR6):​c.817G>T​(p.Val273Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4	c.817G>T	p.Val273Phe	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1	c.817G>T	p.Val273Phe	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6	c.817G>T	p.Val273Phe	missense_variant	3/3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10	c.817G>T	p.Val273Phe	missense_variant	3/3	1	NM_031409.4	ENSP00000343952.5
ENSG00000272980	ENST00000705249.1	c.*770G>T		3_prime_UTR_variant	13/13			ENSP00000516101.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

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

Jul 26, 2024

The c.817G>T (p.V273F) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a G to T substitution at nucleotide position 817, causing the valine (V) at amino acid position 273 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	0.28
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;T;T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.030
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T;.;.;.
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.4	M;M;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.0	D;.;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0060	D;.;D;D
Sift4G	Uncertain	0.0050	D;.;D;D
Polyphen		0.95	P;P;P;P
Vest4		0.60
MutPred		0.65		Loss of stability (P = 0.0304);Loss of stability (P = 0.0304);Loss of stability (P = 0.0304);Loss of stability (P = 0.0304);
MVP		0.90
MPC		1.7
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.51
gMVP		0.70

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: chr6-167550535;