chr7-141972905-G-A

Position:

• chr7-141972905-G-A

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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=6.9996604E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R38	NM_176817.5	c.785C>T	p.Ala262Val	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.785C>T	p.Ala262Val	missense_variant	1/1		NM_176817.5	ENSP00000448219	P1
MGAM	ENST00000465654.5	c.-3+26908G>A		intron_variant		3		ENSP00000419372

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

GnomAD3 exomes AF: 0.499 AC: 125330 AN: 251078 Hom.: 33291 AF XY: 0.515 AC XY: 69949 AN XY: 135696

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 SAS exome AF: 0.635

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

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.634

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.513

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

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.448

Alfa AF: 0.526 Hom.: 48956

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 v4.3

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
MutationTaster	Benign	1.0	P
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

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

Publications

LitVar

Other links and lift over

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