rs10246939

Positions:

• chr7-141972804-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -2.77

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]

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]

ACMG classification

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	Protein	UniProt
TAS2R38	NM_176817.5	c.886A>G	p.Ile296Val	missense_variant	1/1	ENST00000547270.1	NP_789787.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R38	ENST00000547270.1	c.886A>G	p.Ile296Val	missense_variant	1/1		NM_176817.5	ENSP00000448219	P1
MGAM	ENST00000465654.5	c.-3+26807T>C		intron_variant		3		ENSP00000419372

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71975 AN: 151758 Hom.: 17461 Cov.: 32

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

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.: 67 AF XY: 0.452 AC XY: 328817 AN XY: 727234

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.: 32 AF XY: 0.474 AC XY: 35208 AN XY: 74230

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

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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.061
DANN	Benign	0.90
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.15
Sift	Benign	0.23	T
Sift4G	Benign	0.12	T
Polyphen		0.75	P
Vest4		0.033
MPC		0.17
ClinPred		0.040	T
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

Other links and lift over

dbSNP: rs10246939; hg19: chr7-141672604; COSMIC: COSV71885881;