chr7-80458698-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001102386.3(GNAT3):ā€‹c.1038G>Cā€‹(p.Glu346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,581,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

GNAT3
NM_001102386.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.701
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29572895).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNAT3NM_001102386.3 linkuse as main transcriptc.1038G>C p.Glu346Asp missense_variant 8/8 ENST00000398291.4 NP_001095856.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GNAT3ENST00000398291.4 linkuse as main transcriptc.1038G>C p.Glu346Asp missense_variant 8/81 NM_001102386.3 ENSP00000381339 P1
CD36ENST00000435819.5 linkuse as main transcriptc.-477-27769C>G intron_variant 2 ENSP00000399421 P1P16671-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152120
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1428998
Hom.:
0
Cov.:
28
AF XY:
0.00000141
AC XY:
1
AN XY:
709534
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000258
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000338
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152120
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000680

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 18, 2023The c.1038G>C (p.E346D) alteration is located in exon 8 (coding exon 8) of the GNAT3 gene. This alteration results from a G to C substitution at nucleotide position 1038, causing the glutamic acid (E) at amino acid position 346 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.074
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
0.95
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
0.25
N
REVEL
Benign
0.27
Sift
Benign
0.033
D
Sift4G
Benign
0.42
T
Polyphen
0.26
B
Vest4
0.41
MutPred
0.40
Loss of ubiquitination at K349 (P = 0.1079);
MVP
0.75
MPC
0.041
ClinPred
0.46
T
GERP RS
3.6
Varity_R
0.15
gMVP
0.53

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs192064811; hg19: chr7-80088014; API