NM_001102386.3:c.1014A>G

Variant names:

• chr7-80458722-T-C
• rs144189518
• NM_001102386.3:c.1014A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001102386.3(GNAT3):​c.1014A>G​(p.Ala338Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,597,044 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (6 hom., cov: 33)
  • Exomes 𝑓: 0.012 (144 hom.)
• Consequence: GNAT3 NM_001102386.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 2 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-80458722-T-C is Benign according to our data. Variant chr7-80458722-T-C is described in ClinVar as Benign. ClinVar VariationId is 3777778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102386.3. 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
	GNAT3	NM_001102386.3	MANE Select	c.1014A>G	p.Ala338Ala	synonymous	Exon 8 of 8	NP_001095856.1	A8MTJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT3	ENST00000398291.4	TSL:1 MANE Select	c.1014A>G	p.Ala338Ala	synonymous	Exon 8 of 8	ENSP00000381339.3	A8MTJ3
	CD36	ENST00000435819.5	TSL:2	c.-477-27745T>C		intron	N/A	ENSP00000399421.1	P16671-1
	CD36	ENST00000956914.1		c.-477-27745T>C		intron	N/A	ENSP00000626973.1

Frequencies

GnomAD3 genomes AF: 0.00800 AC: 1218 AN: 152166 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00904 AC: 2079 AN: 229974 AF XY: 0.00860

Gnomad AFR exome AF: 0.00236

Gnomad AMR exome AF: 0.00810

Gnomad ASJ exome AF: 0.00393

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00707

Gnomad NFE exome AF: 0.0145

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0120 AC: 17279 AN: 1444760 Hom.: 144 Cov.: 28 AF XY: 0.0116 AC XY: 8339 AN XY: 717670

African (AFR) AF: 0.00204 AC: 67 AN: 32878

American (AMR) AF: 0.00876 AC: 372 AN: 42452

Ashkenazi Jewish (ASJ) AF: 0.00310 AC: 80 AN: 25844

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39340

South Asian (SAS) AF: 0.000856 AC: 71 AN: 82924

European-Finnish (FIN) AF: 0.00786 AC: 416 AN: 52902

Middle Eastern (MID) AF: 0.000872 AC: 5 AN: 5734

European-Non Finnish (NFE) AF: 0.0142 AC: 15629 AN: 1102878

Other (OTH) AF: 0.0107 AC: 637 AN: 59808

GnomAD4 genome AF: 0.00799 AC: 1217 AN: 152284 Hom.: 6 Cov.: 33 AF XY: 0.00688 AC XY: 512 AN XY: 74454

African (AFR) AF: 0.00286 AC: 119 AN: 41564

American (AMR) AF: 0.00647 AC: 99 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 905 AN: 68020

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00881 Hom.: 26

Bravo AF: 0.00825

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.9
DANN	Benign	0.69
PhyloP100		-0.062
Mutation Taster		=91/9	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: rs144189518; hg19: chr7-80088038;