Variant chr7-141972905-G-A 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.785C>T(p.Ala262Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,613,670 control chromosomes in the GnomAD database, including 234,660 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.47 ( 17884 hom., cov: 30)

Exomes 𝑓: 0.54 ( 216776 hom. )

Consequence

TAS2R38
NM_176817.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

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=6.9996604E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R38	NM_176817.5 link	c.785C>T	p.Ala262Val	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.785C>T	p.Ala262Val	missense_variant	Exon 1 of 1	6	NM_176817.5	ENSP00000448219.1		P59533
MGAM	ENST00000465654.5 link	c.-3+26908G>A		intron_variant	Intron 2 of 5	3		ENSP00000419372.1		E7EW87

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71667

AN:

151720

Hom.:

17877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.760

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.499

AC:

125330

AN:

251078

Hom.:

33291

AF XY:

0.515

AC XY:

69949

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.540

AC:

788886

AN:

1461832

Hom.:

216776

Cov.:

AF XY:

0.543

AC XY:

395198

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.316

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.620

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.472

AC:

71688

AN:

151838

Hom.:

17884

Cov.:

AF XY:

0.474

AC XY:

35175

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.365

Gnomad4 ASJ

AF:

0.492

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.448

Alfa

AF:

0.526

Hom.:

48956

Bravo

AF:

0.440

TwinsUK

AF:

0.550

AC:

2040

ALSPAC

AF:

0.551

AC:

2122

ESP6500AA

AF:

0.341

AC:

1504

ESP6500EA

AF:

0.545

AC:

4683

ExAC

AF:

0.507

AC:

61557

Asia WGS

AF:

0.492

AC:

1712

AN:

3478

EpiCase

AF:

0.530

EpiControl

AF:

0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0000070

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

REVEL

Benign

0.040

Sift

Benign

0.041

Sift4G

Benign

0.54

Polyphen

0.097

Vest4

0.063

MPC

0.42

ClinPred

0.0070

GERP RS

2.9

Varity_R

0.063

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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