7-141973545-C-G

Position:

• chr7-141973545-C-G

Variant summary

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

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. 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 0.45 (15588 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129803 hom.)
• Consequence: TAS2R38 NM_176817.5 missense
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 2.99

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=1.0074259E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R38	NM_176817.5	c.145G>C	p.Ala49Pro	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.145G>C	p.Ala49Pro	missense_variant	1/1	6	NM_176817.5	ENSP00000448219.1
MGAM	ENST00000465654.5	c.-3+27548C>G		intron_variant		3		ENSP00000419372.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67828 AN: 151756 Hom.: 15564 Cov.: 31

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

GnomAD3 exomes AF: 0.458 AC: 115118 AN: 251274 Hom.: 28227 AF XY: 0.445 AC XY: 60404 AN XY: 135802

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 SAS exome AF: 0.346

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.: 67 AF XY: 0.413 AC XY: 300431 AN XY: 727204

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.447 AC: 67893 AN: 151874 Hom.: 15588 Cov.: 31 AF XY: 0.448 AC XY: 33254 AN XY: 74224

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.484

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

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

Dec 30, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.5	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.088
Sift	Benign	0.31	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.030
MPC		0.26
ClinPred		0.0069	T
GERP RS		5.1
Varity_R		0.14
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs713598; hg19: chr7-141673345; COSMIC: COSV71885858;