NM_006564.2:c.552C>T

Variant names:

• chr3-45947033-C-T
• rs61751654
• NM_006564.2:c.552C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006564.2(CXCR6):​c.552C>T​(p.Asp184Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,614,196 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (33 hom.)
• Consequence: CXCR6 NM_006564.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.98
• Publications: 4 publications found

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]

FYCO1 Gene-Disease associations (from GenCC):

• cataract 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-45947033-C-T is Benign according to our data. Variant chr3-45947033-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 771134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006564.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR6	NM_006564.2	MANE Select	c.552C>T	p.Asp184Asp	synonymous	Exon 2 of 2	NP_006555.1	A0N0N3
	FYCO1	NM_024513.4	MANE Select	c.3944+8216G>A		intron	N/A	NP_078789.2	Q9BQS8-1
	CXCR6	NM_001386435.1		c.552C>T	p.Asp184Asp	synonymous	Exon 2 of 2	NP_001373364.1	O00574

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR6	ENST00000304552.5	TSL:1 MANE Select	c.552C>T	p.Asp184Asp	synonymous	Exon 2 of 2	ENSP00000304414.4	O00574
	CXCR6	ENST00000457814.1	TSL:1	c.552C>T	p.Asp184Asp	synonymous	Exon 2 of 2	ENSP00000396886.1	O00574
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.3944+8216G>A		intron	N/A	ENSP00000296137.2	Q9BQS8-1

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152194 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00582

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00416 AC: 1045 AN: 251446 AF XY: 0.00414

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00587

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00570 AC: 8334 AN: 1461884 Hom.: 33 Cov.: 32 AF XY: 0.00554 AC XY: 4031 AN XY: 727242

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00496 AC: 222 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 282 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86256

European-Finnish (FIN) AF: 0.00165 AC: 88 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.00651 AC: 7243 AN: 1112006

Other (OTH) AF: 0.00692 AC: 418 AN: 60394

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152312 Hom.: 5 Cov.: 32 AF XY: 0.00418 AC XY: 311 AN XY: 74476

African (AFR) AF: 0.00120 AC: 50 AN: 41578

American (AMR) AF: 0.00817 AC: 125 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00582 AC: 396 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00494 Hom.: 2

Bravo AF: 0.00471

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00676

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.027
DANN	Benign	0.42
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61751654; hg19: chr3-45988525;