Variant 7-141972804-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_176817.5(TAS2R38):c.886A>G(p.Ile296Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,613,728 control chromosomes in the GnomAD database, including 171,814 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.47 ( 17488 hom., cov: 32)

Exomes 𝑓: 0.46 ( 154326 hom. )

Consequence

TAS2R38
NM_176817.5 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -2.77

Variant links:

Genes affected

TAS2R38 (HGNC:9584): (taste 2 receptor member 38) This gene encodes a seven-transmembrane G protein-coupled receptor that controls the ability to taste glucosinolates, a family of bitter-tasting compounds found in plants of the Brassica sp. Synthetic compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) have been identified as ligands for this receptor and have been used to test the genetic diversity of this gene. Although several allelic forms of this gene have been identified worldwide, there are two predominant common forms (taster and non-taster) found outside of Africa. These alleles differ at three nucleotide positions resulting in amino acid changes in the protein (A49P, A262V, and V296I) with the amino acid combination PAV identifying the taster variant (and AVI identifying the non-taster variant). [provided by RefSeq, Oct 2009]

TAS2R38 links:

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MGAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5128236E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R38	NM_176817.5 linkuse as main transcript	c.886A>G	p.Ile296Val	missense_variant	1/1	ENST00000547270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R38	ENST00000547270.1 linkuse as main transcript	c.886A>G	p.Ile296Val	missense_variant	1/1		NM_176817.5	P1
MGAM	ENST00000465654.5 linkuse as main transcript	c.-3+26807T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

71975

AN:

151758

Hom.:

17461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.509

GnomAD3 exomes

AF:

0.487

AC:

122223

AN:

250890

Hom.:

31428

AF XY:

0.475

AC XY:

64366

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.676

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.455

AC:

665414

AN:

1461852

Hom.:

154326

Cov.:

AF XY:

0.452

AC XY:

328817

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.505

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.448

Gnomad4 OTH exome

AF:

0.476

GnomAD4 genome

AF:

0.474

AC:

72044

AN:

151876

Hom.:

17488

Cov.:

AF XY:

0.474

AC XY:

35208

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.669

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.511

Alfa

AF:

0.465

Hom.:

38395

Bravo

AF:

0.499

TwinsUK

AF:

0.450

AC:

1670

ALSPAC

AF:

0.450

AC:

1735

ESP6500AA

AF:

0.478

AC:

2106

ESP6500EA

AF:

0.456

AC:

3918

ExAC

AF:

0.476

AC:

57764

Asia WGS

AF:

0.497

AC:

1728

AN:

3478

EpiCase

AF:

0.470

EpiControl

AF:

0.472

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Phenylthiocarbamide tasting

Other:1

drug response, no assertion criteria provided

literature only

OMIM

May 12, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.061

DANN

Benign

0.90

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.46

MetaRNN

Benign

0.000025

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.79

REVEL

Benign

0.15

Sift

Benign

0.23

Sift4G

Benign

0.12

Polyphen

0.75

Vest4

0.033

MPC

0.17

ClinPred

0.040

GERP RS

0.98

Varity_R

0.023

gMVP

0.064

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over