NM_176817.5:c.886A>G

Variant names:

• chr7-141972804-T-C
• rs10246939
• NM_176817.5:c.886A>G
• TAS2R38 p.Ile296Val

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -10 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Moderate

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 cumulative frequency of 0.457 (AC=737,458) in the gnomAD database across 1,613,728 control chromosomes, including 171,814 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.675. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars). This exact variant is curated in the UniProt human variants database as Uncertain Significance.

• 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
• Publications: 100 publications found

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 Gene-Disease associations (from GenCC):

• thiourea tasting

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -10 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6750 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_176817.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TAS2R38 NM_176817.5	MANE Select	c.886A>G p.Ile296Val	missense	Exon 1 of 1	Prot: NP_789787.5 UniProt:

TAS2R38 NM_176817.5

MANE Select

HGVSc / HGVSpc.886A>Gp.Ile296Val

Exon rankExon 1 of 1

missense

Prot: NP_789787.5UniProt: P59533

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TAS2R38 ENST00000547270.1	TSL:6MANE Select	c.886A>G p.Ile296Val	missense	Exon 1 of 1	Prot: ENSP00000448219.1 UniProt:
	MGAM ENST00000465654.5	TSL:3	c.-3+26807T>C	intron	Intron 2 of 5	Prot: ENSP00000419372.1 UniProt:

TAS2R38 ENST00000547270.1

TSL:6MANE Select

HGVSc / HGVSpc.886A>Gp.Ile296Val

Exon rankExon 1 of 1

missense

Prot: ENSP00000448219.1UniProt: P59533

MGAM ENST00000465654.5

TSL:3

HGVSc / HGVSpc.-3+26807T>C

Exon rankIntron 2 of 5

intron

Prot: ENSP00000419372.1UniProt: E7EW87

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.474	AC:71975	Hom:17461	AN:151758	Cov:32
GnomAD2 exomes	AF: 0.487	AC:122223	Hom:	AN:250890	Cov:
GnomAD4 exome	AF: 0.455	AC:665414	Hom:154326	AN:1461852	Cov:67
GnomAD4 genome	AF: 0.474	AC:72044	Hom:17488	AN:151876	Cov:32
TOPMed (Bravo)	AF: 0.499	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.467	AC:348744	Hom:82574	AN:746870	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.520	AC:1219	Hom:331	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.679	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.467	AC:140	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.463	AC:6024	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.497	AC:1728	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.592	AC:4279	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.418	AC:841	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.576	AC:70719	Hom:20471	AN:122732	Cov:
Turkish Variome	AF: 0.506	AC:3384	Hom:886	AN:6694	Cov:
UK10K	AF: 0.450	AC:3405	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.677	AC:6067	Hom:2054	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.422 *	4688	11106	0.422 *	7429	17612
BipEx(Bipolar disorder (including schizoaffective))	0.438	12450	28420	0.434	12511	28844
Epi25(Epilepsy)	0.479	20102	41958	0.480	32119	66886
SCHEMA(Schizophrenia)	0.512	84737	165522	0.514	142639	277438

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Phenylthiocarbamide tasting (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	11
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
FuncVEP CTI	Benign	0.035
GPN-Star LLR	N/A	1.4
GPN-Star score	N/A	-1.4
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.93	T
Mutation Taster	N/A	100/0	polymorphism (auto)
MutationAssessor	Uncertain	2.2	M
PhyloP100	Benign	-2.8
popEVE	Benign	-3.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.15
Sift	Benign	0.23	T
Sift4G	Benign	0.12	T
Varity_R	N/A	0.023
VESM-3B	Benign	-3.7

Showing 27 of 27 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs10246939;

hg19: chr7-141672604;

COSMIC: COSV71885881;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar