7-80468260-A-G

Variant names:

• chr7-80468260-A-G
• rs799929
• NM_001102386.3:c.591-5629T>C

Variant summary

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

The NM_001102386.3(GNAT3):​c.591-5629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,726 control chromosomes in the GnomAD database, including 7,539 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 0.30 (7539 hom., cov: 32)
• Consequence: GNAT3 NM_001102386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAT3	NM_001102386.3	c.591-5629T>C		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.591-5629T>C		intron_variant	Intron 5 of 7	1	NM_001102386.3	ENSP00000381339.3
CD36	ENST00000435819.5	c.-477-18207A>G		intron_variant	Intron 1 of 16	2		ENSP00000399421.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46034 AN: 151608 Hom.: 7542 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.304 AC: 46059 AN: 151726 Hom.: 7539 Cov.: 32 AF XY: 0.309 AC XY: 22915 AN XY: 74104

African (AFR) AF: 0.217 AC: 8990 AN: 41340

American (AMR) AF: 0.368 AC: 5600 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3464

East Asian (EAS) AF: 0.598 AC: 3079 AN: 5152

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4025 AN: 10556

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20916 AN: 67866

Other (OTH) AF: 0.295 AC: 621 AN: 2106

Alfa AF: 0.280 Hom.: 3110

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		0.19
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: rs799929; hg19: chr7-80097576;