Variant 12-11061546-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_176887.2(TAS2R46):c.749G>A(p.Trp250*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,606,394 control chromosomes in the GnomAD database, including 32,709 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 0.20 ( 398 hom., cov: 37)

Exomes 𝑓: 0.23 ( 32311 hom. )

Consequence

TAS2R46
NM_176887.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.445

Variant links:

Genes affected

TAS2R46 (HGNC:18877): (taste 2 receptor member 46) TAS2R46 belongs to the large TAS2R receptor family. TAS2Rs are expressed on the surface of taste receptor cells and mediate the perception of bitterness through a G protein-coupled second messenger pathway (Conte et al., 2002 [PubMed 12584440]). For further information on TAS2Rs, see MIM 604791.[supplied by OMIM, Sep 2009]

TAS2R46 links:

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

PRH1 links:

PRH1-TAS2R14 (HGNC:):

PRH1-TAS2R14 links:

TAS2R14 (HGNC:14920): (taste 2 receptor member 14) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

TAS2R14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R46	NM_176887.2 link	c.749G>A	p.Trp250*	stop_gained	1/1	ENST00000533467.1	NP_795368.2	P59540

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R46	ENST00000533467.1 link	c.749G>A	p.Trp250*	stop_gained	1/1	6	NM_176887.2	ENSP00000436450.1		P59540

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30776

AN:

151568

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.228

AC:

57076

AN:

250882

Hom.:

6636

AF XY:

0.225

AC XY:

30559

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.211

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.228

AC:

330957

AN:

1454708

Hom.:

32311

Cov.:

AF XY:

0.226

AC XY:

163261

AN XY:

723716

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.203

AC:

30784

AN:

151686

Hom.:

398

Cov.:

AF XY:

0.204

AC XY:

15168

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.220

Hom.:

2492

TwinsUK

AF:

0.236

AC:

875

ALSPAC

AF:

0.249

AC:

958

ESP6500AA

AF:

0.229

AC:

1007

ESP6500EA

AF:

0.227

AC:

1953

ExAC

AF:

0.226

AC:

27438

Asia WGS

AF:

0.235

AC:

818

AN:

3478

EpiCase

AF:

0.223

EpiControl

AF:

0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Benign

0.73

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.015

Vest4

0.030

GERP RS

-0.023

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over