7-141972804-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

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

Publications

227 publications found

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 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MGAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAS2R38	NM_176817.5 link	c.886A>G	p.Ile296Val	missense_variant	Exon 1 of 1	ENST00000547270.1	NP_789787.5	P59533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R38	ENST00000547270.1 link	c.886A>G	p.Ile296Val	missense_variant	Exon 1 of 1	6	NM_176817.5	ENSP00000448219.1		P59533
MGAM	ENST00000465654.5 link	c.-3+26807T>C		intron_variant	Intron 2 of 5	3		ENSP00000419372.1		E7EW87

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

GnomAD2 exomes

AF:

0.487

AC:

122223

AN:

250890

AF XY:

0.475

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 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

African (AFR)

AF:

0.491

AC:

16455

AN:

33480

American (AMR)

AF:

0.681

AC:

30474

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

13187

AN:

26136

East Asian (EAS)

AF:

0.611

AC:

24244

AN:

39698

South Asian (SAS)

AF:

0.366

AC:

31572

AN:

86258

European-Finnish (FIN)

AF:

0.380

AC:

20314

AN:

53412

Middle Eastern (MID)

AF:

0.472

AC:

2723

AN:

5768

European-Non Finnish (NFE)

AF:

0.448

AC:

497684

AN:

1111984

Other (OTH)

AF:

0.476

AC:

28761

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

23003

46006

69008

92011

115014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.474

AC:

72044

AN:

151876

Hom.:

17488

Cov.:

AF XY:

0.474

AC XY:

35208

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.484

AC:

20037

AN:

41390

American (AMR)

AF:

0.616

AC:

9383

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1763

AN:

3466

East Asian (EAS)

AF:

0.669

AC:

3442

AN:

5148

South Asian (SAS)

AF:

0.358

AC:

1722

AN:

4812

European-Finnish (FIN)

AF:

0.374

AC:

3946

AN:

10550

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30308

AN:

67970

Other (OTH)

AF:

0.511

AC:

1073

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1932

3863

5795

7726

9658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.466

Hom.:

78145

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

May 12, 2011

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

-2.8

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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7-141972804-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over