7-141972802-GAT-AAC

Variant names:

• chr7-141972802-GAT-AAC
• NM_176817.5:c.886_888delATCinsGTT
• TAS2R38 p.Ile296Val

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_176817.5(TAS2R38):c.886_888delATCinsGTT (p.Ile296Val) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant has a gnomAD grpmax filtering allele frequency (95% CI) of 0.00000398, indicating it is observed in the general population. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.I296V: drug_response (ClinVar VariationId 2906, 0 stars) This exact variant is curated in the UniProt human variants database as Uncertain Significance.

• Frequency: GnomAD MNV: 𝑓 0.0000040 Genomes: not found (cov: 32)
• Consequence: TAS2R38 NM_176817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 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: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AD/XL gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000398 — very rare for AD/XL gene (threshold 0.0001) — PM2 moderate.

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.886_888delATCinsGTT p.Ile296Val	missense	N/A	Prot: NP_789787.5 UniProt:

TAS2R38 NM_176817.5

MANE Select

HGVSc / HGVSpc.886_888delATCinsGTTp.Ile296Val

Exon rankN/A

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.886_888delATCinsGTT p.Ile296Val	missense	N/A	Prot: ENSP00000448219.1 UniProt:
	MGAM ENST00000465654.5	TSL:3	c.-3+26805_-3+26807delGATinsAAC	intron	Intron 2 of 5	Prot: ENSP00000419372.1 UniProt:

TAS2R38 ENST00000547270.1

TSL:6MANE Select

HGVSc / HGVSpc.886_888delATCinsGTTp.Ile296Val

Exon rankN/A

missense

Prot: ENSP00000448219.1UniProt: P59533

MGAM ENST00000465654.5

TSL:3

HGVSc / HGVSpc.-3+26805_-3+26807delGATinsAAC

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
GnomAD MNV	AF: 0.00000398	AC:1	Hom:0	AN:	Cov:

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	4.0

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr7-141672602;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

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