rs6942728

Variant names:

• chr7-80465612-T-C
• rs6942728
• NM_001102386.3:c.591-2981A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102386.3(GNAT3):​c.591-2981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,102 control chromosomes in the GnomAD database, including 1,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1001 hom., cov: 32)
• Consequence: GNAT3 NM_001102386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 1 publications found

Genes affected

GNAT3 (HGNC:22800): (G protein subunit alpha transducin 3) Sweet, bitter, and umami tastes are transmitted from taste receptors by a specific guanine nucleotide binding protein. The protein encoded by this gene is the alpha subunit of this heterotrimeric G protein, which is found not only in the oral epithelium but also in gut tissues. Variations in this gene have been linked to metabolic syndrome. [provided by RefSeq, Dec 2015]

CD36 (HGNC:1663): (CD36 molecule (CD36 blood group)) The protein encoded by this gene is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets and various cell lines. Since thrombospondins are widely distributed proteins involved in a variety of adhesive processes, this protein may have important functions as a cell adhesion molecule. It binds to collagen, thrombospondin, anionic phospholipids and oxidized LDL. It directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and it binds long chain fatty acids and may function in the transport and/or as a regulator of fatty acid transport. Mutations in this gene cause platelet glycoprotein deficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2014]

CD36 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAT3	NM_001102386.3	c.591-2981A>G		intron_variant	Intron 5 of 7	ENST00000398291.4	NP_001095856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAT3	ENST00000398291.4	c.591-2981A>G		intron_variant	Intron 5 of 7	1	NM_001102386.3	ENSP00000381339.3
CD36	ENST00000435819.5	c.-477-20855T>C		intron_variant	Intron 1 of 16	2		ENSP00000399421.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16996 AN: 151984 Hom.: 1003 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 16992 AN: 152102 Hom.: 1001 Cov.: 32 AF XY: 0.108 AC XY: 8046 AN XY: 74360

African (AFR) AF: 0.129 AC: 5371 AN: 41528

American (AMR) AF: 0.0928 AC: 1415 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4820

European-Finnish (FIN) AF: 0.0931 AC: 986 AN: 10594

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8186 AN: 67966

Other (OTH) AF: 0.110 AC: 232 AN: 2104

Alfa AF: 0.117 Hom.: 618

Bravo AF: 0.111

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs6942728; hg19: chr7-80094928;