Menu
GeneBe

3-45947490-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006564.2(CXCR6):c.1009A>C(p.Thr337Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CXCR6
NM_006564.2 missense

Scores

2
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35
Variant links:
Genes affected
CXCR6 (HGNC:16647): (C-X-C motif chemokine receptor 6) The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the CXC chemokine receptor family. This family also includes CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, and CXCR7. This gene, which maps to the chemokine receptor gene cluster, is expressed in several T lymphocyte subsets and bone marrow stromal cells. The encoded protein and its exclusive ligand, chemokine ligand 16 (CCL16), are part of a signalling pathway that regulates T lymphocyte migration to various peripheral tissues (the liver, spleen red pulp, intestine, lungs, and skin) and promotes cell-cell interaction with dendritic cells and fibroblastic reticular cells. CXCR6/CCL16 also controls the localization of resident memory T lymphocytes to different compartments of the lung and maintains airway resident memory T lymphocytes, which are an important first line of defense against respiratory pathogens. The encoded protein serves as an entry coreceptor used by HIV-1 and SIV to enter target cells, in conjunction with CD4. [provided by RefSeq, Aug 2020]
FYCO1 (HGNC:14673): (FYVE and coiled-coil domain autophagy adaptor 1) The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3581829).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCR6NM_006564.2 linkuse as main transcriptc.1009A>C p.Thr337Pro missense_variant 2/2 ENST00000304552.5
FYCO1NM_024513.4 linkuse as main transcriptc.3944+7759T>G intron_variant ENST00000296137.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCR6ENST00000304552.5 linkuse as main transcriptc.1009A>C p.Thr337Pro missense_variant 2/21 NM_006564.2 P1
FYCO1ENST00000296137.7 linkuse as main transcriptc.3944+7759T>G intron_variant 1 NM_024513.4 P1Q9BQS8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsOct 26, 2022The c.1009A>C (p.T337P) alteration is located in exon 2 (coding exon 1) of the CXCR6 gene. This alteration results from a A to C substitution at nucleotide position 1009, causing the threonine (T) at amino acid position 337 to be replaced by a proline (P). 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
0.091
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.36
T;T;T;T
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Uncertain
2.1
M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.5
D;D;D;D
REVEL
Uncertain
0.31
Sift
Benign
0.039
D;D;D;D
Sift4G
Uncertain
0.032
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.31
MutPred
0.23
Loss of glycosylation at T337 (P = 0.043);Loss of glycosylation at T337 (P = 0.043);Loss of glycosylation at T337 (P = 0.043);Loss of glycosylation at T337 (P = 0.043);
MVP
0.84
MPC
1.3
ClinPred
0.98
D
GERP RS
5.6
Varity_R
0.74
gMVP
0.54

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: chr3-45988982; API