rs6975345

Positions:

• chr7-80494683-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102386.3(GNAT3):​c.119-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,219,388 control chromosomes in the GnomAD database, including 24,585 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 0.27 (10283 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14302 hom.)
• Consequence: GNAT3 NM_001102386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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]

LOC107986812 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAT3	NM_001102386.3	c.119-36A>G		intron_variant		ENST00000398291.4
LOC107986812	XR_001745252.2	n.217+6902T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAT3	ENST00000398291.4	c.119-36A>G		intron_variant		1	NM_001102386.3	P1
CD36	ENST00000435819.5	c.-261+6902T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41382 AN: 152020 Hom.: 10253 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.151 AC: 24619 AN: 163108 Hom.: 3384 AF XY: 0.145 AC XY: 12433 AN XY: 85938

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.0958

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0863

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.135 AC: 143706 AN: 1067250 Hom.: 14302 Cov.: 14 AF XY: 0.132 AC XY: 71681 AN XY: 541684

Gnomad4 AFR exome AF: 0.689

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0882

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.273 AC: 41466 AN: 152138 Hom.: 10283 Cov.: 32 AF XY: 0.265 AC XY: 19695 AN XY: 74370

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.221

Alfa AF: 0.139 Hom.: 3605

Bravo AF: 0.294

Asia WGS AF: 0.162 AC: 564 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.64

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: rs6975345; hg19: chr7-80123999; COSMIC: COSV68068852;