Variant 6-167136379-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_031409.4(CCR6):c.149C>T(p.Pro50Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,862 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: 0.0000055 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

Variant links:

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]

CCR6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR6	NM_031409.4 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCR6	ENST00000341935.10 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/3	1	NM_031409.4	ENSP00000343952	P1
CCR6	ENST00000349984.6 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	4/4	1		ENSP00000339393	P1
CCR6	ENST00000400926.5 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/3	2		ENSP00000383715	P1
CCR6	ENST00000643861.1 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	4/4			ENSP00000493637	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251208

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.149C>T (p.P50L) 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 149, causing the proline (P) at amino acid position 50 to be replaced by a leucine (L). 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

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

.;T;T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.81

T;T;.;.;.

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.94

D;D;D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

.;M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.2

.;D;.;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.12

.;T;.;T;T

Sift4G

Benign

0.17

.;T;.;T;T

Polyphen

0.99

.;D;D;D;D

Vest4

0.66, 0.66, 0.66

MutPred

0.75

Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);

MVP

0.76

MPC

1.5

ClinPred

0.94

GERP RS

4.7

Varity_R

0.36

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over