3-45947033-C-T

Position:

• chr3-45947033-C-T

Variant summary

Our verdict is Benign. Variant got -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 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 criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.98

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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]. Clinvar id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR6	NM_006564.2	c.552C>T	p.Asp184Asp	synonymous_variant	2/2	ENST00000304552.5	NP_006555.1
FYCO1	NM_024513.4	c.3944+8216G>A		intron_variant		ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR6	ENST00000304552.5	c.552C>T	p.Asp184Asp	synonymous_variant	2/2	1	NM_006564.2	ENSP00000304414.4
FYCO1	ENST00000296137.7	c.3944+8216G>A		intron_variant		1	NM_024513.4	ENSP00000296137.2

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

GnomAD3 exomes AF: 0.00416 AC: 1045 AN: 251446 Hom.: 0 AF XY: 0.00414 AC XY: 562 AN XY: 135882

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 SAS exome AF: 0.000457

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

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00165

Gnomad4 NFE exome AF: 0.00651

Gnomad4 OTH exome AF: 0.00692

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

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00582

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00499 Hom.: 2

Bravo AF: 0.00471

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00676

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.027
DANN	Benign	0.42

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: rs61751654; hg19: chr3-45988525;