rs1726866

Variant names:

• chr7-141972905-G-A
• rs1726866
• NM_176817.5:c.785C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-141972905-G-A
• chr7-141972905-G-C
• chr7-141972905-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17884 hom., cov: 30)
  • Exomes 𝑓: 0.54 (216776 hom.)
• Consequence: TAS2R38 NM_176817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 209 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]

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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R38	NM_176817.5	MANE Select	c.785C>T	p.Ala262Val	missense	Exon 1 of 1	NP_789787.5	P59533

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R38	ENST00000547270.1	TSL:6 MANE Select	c.785C>T	p.Ala262Val	missense	Exon 1 of 1	ENSP00000448219.1	P59533
	MGAM	ENST00000465654.5	TSL:3	c.-3+26908G>A		intron	N/A	ENSP00000419372.1	E7EW87

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71667 AN: 151720 Hom.: 17877 Cov.: 30

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

GnomAD2 exomes AF: 0.499 AC: 125330 AN: 251078 AF XY: 0.515

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 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.: 72 AF XY: 0.543 AC XY: 395198 AN XY: 727214

African (AFR) AF: 0.316 AC: 10569 AN: 33480

American (AMR) AF: 0.310 AC: 13851 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12947 AN: 26136

East Asian (EAS) AF: 0.389 AC: 15457 AN: 39698

South Asian (SAS) AF: 0.634 AC: 54661 AN: 86258

European-Finnish (FIN) AF: 0.620 AC: 33104 AN: 53418

Middle Eastern (MID) AF: 0.520 AC: 2998 AN: 5768

European-Non Finnish (NFE) AF: 0.552 AC: 614309 AN: 1111960

Other (OTH) AF: 0.513 AC: 30990 AN: 60396

GnomAD4 genome AF: 0.472 AC: 71688 AN: 151838 Hom.: 17884 Cov.: 30 AF XY: 0.474 AC XY: 35175 AN XY: 74192

African (AFR) AF: 0.329 AC: 13612 AN: 41384

American (AMR) AF: 0.365 AC: 5571 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1701 AN: 5140

South Asian (SAS) AF: 0.642 AC: 3082 AN: 4804

European-Finnish (FIN) AF: 0.626 AC: 6588 AN: 10526

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37654 AN: 67946

Other (OTH) AF: 0.448 AC: 945 AN: 2108

Alfa AF: 0.520 Hom.: 94846

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0000070	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.040
Sift	Benign	0.041	D
Sift4G	Benign	0.54	T
Polyphen		0.097	B
Vest4		0.063
MPC		0.42
ClinPred		0.0070	T
GERP RS		2.9
Varity_R		0.063
gMVP		0.072
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1726866; hg19: chr7-141672705; COSMIC: COSV71885170;