chr7-141973545-C-G

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.145G>C(p.Ala49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,613,688 control chromosomes in the GnomAD database, including 145,391 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 0.45 ( 15588 hom., cov: 31)

Exomes 𝑓: 0.42 ( 129803 hom. )

Consequence

TAS2R38
NM_176817.5 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 2.99

Publications

240 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=1.0074259E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176817.5. 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
	TAS2R38	NM_176817.5	MANE Select	c.145G>C	p.Ala49Pro	missense	Exon 1 of 1	NP_789787.5	P59533

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R38	ENST00000547270.1	TSL:6 MANE Select	c.145G>C	p.Ala49Pro	missense	Exon 1 of 1	ENSP00000448219.1	P59533
	MGAM	ENST00000465654.5	TSL:3	c.-3+27548C>G		intron	N/A	ENSP00000419372.1	E7EW87

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67828

AN:

151756

Hom.:

15564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.482

GnomAD2 exomes

AF:

0.458

AC:

115118

AN:

251274

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.672

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.416

AC:

608123

AN:

1461814

Hom.:

129803

Cov.:

AF XY:

0.413

AC XY:

300431

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.485

AC:

16226

AN:

33480

American (AMR)

AF:

0.666

AC:

29778

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

12142

AN:

26134

East Asian (EAS)

AF:

0.610

AC:

24219

AN:

39698

South Asian (SAS)

AF:

0.347

AC:

29918

AN:

86258

European-Finnish (FIN)

AF:

0.355

AC:

18942

AN:

53380

Middle Eastern (MID)

AF:

0.449

AC:

2588

AN:

5766

European-Non Finnish (NFE)

AF:

0.403

AC:

447830

AN:

1111982

Other (OTH)

AF:

0.438

AC:

26480

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

22294

44588

66883

89177

111471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14082

28164

42246

56328

70410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.447

AC:

67893

AN:

151874

Hom.:

15588

Cov.:

AF XY:

0.448

AC XY:

33254

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.475

AC:

19662

AN:

41400

American (AMR)

AF:

0.595

AC:

9083

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1602

AN:

3466

East Asian (EAS)

AF:

0.667

AC:

3430

AN:

5140

South Asian (SAS)

AF:

0.341

AC:

1637

AN:

4802

European-Finnish (FIN)

AF:

0.350

AC:

3688

AN:

10530

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27422

AN:

67944

Other (OTH)

AF:

0.484

AC:

1024

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1895

3790

5686

7581

9476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.422

Hom.:

10500

Bravo

AF:

0.472

TwinsUK

AF:

0.405

AC:

1500

ALSPAC

AF:

0.412

AC:

1589

ESP6500AA

AF:

0.470

AC:

2070

ESP6500EA

AF:

0.410

AC:

3530

ExAC

AF:

0.446

AC:

54121

Asia WGS

AF:

0.490

AC:

1702

AN:

3478

EpiCase

AF:

0.427

EpiControl

AF:

0.429

ClinVar

ClinVar submissions

Significance:drug response

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Phenylthiocarbamide tasting (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.31

MetaRNN

Benign

0.00010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.5

PhyloP100

3.0

PrimateAI

Benign

0.34

PROVEAN

Benign

1.2

REVEL

Benign

0.088

Sift

Benign

0.31

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.030

MPC

0.26

ClinPred

0.0069

GERP RS

5.1

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.14

gMVP

0.29

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over