Variant 12-10997447-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_176889.4(TAS2R20):c.429C>A(p.His143Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,612,850 control chromosomes in the GnomAD database, including 113,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.30 ( 8883 hom., cov: 32)

Exomes 𝑓: 0.36 ( 104814 hom. )

Consequence

TAS2R20
NM_176889.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

TAS2R20 (HGNC:19109): (taste 2 receptor member 20) This gene encodes a member of the taste receptor two family of class C G-protein coupled receptors. Receptors of this family have a short extracellular N-terminus, seven transmembrane helices, three extracellular loops and three intracellular loops, and an intracellular C-terminus. Members of this family are expressed in a subset of taste receptor cells, where they function in bitter taste reception, as well as in non-gustatory cells including those of the brain, reproductive organs, respiratory system, and gastrointestinal system. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2016]

TAS2R20 links:

ENSG00000275778 (HGNC:):

ENSG00000275778 links:

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

PRH1 links:

TAS2R14 (HGNC:14920): (taste 2 receptor member 14) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

TAS2R14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8293484E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R20	NM_176889.4 link	c.429C>A	p.His143Gln	missense_variant	1/1	ENST00000538986.2	NP_795370.2	P59543

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2 link	c.429C>A	p.His143Gln	missense_variant	1/1	6	NM_176889.4	ENSP00000441624.1		P59543
ENSG00000275778	ENST00000703543.1 link	c.-125-23726C>A		intron_variant				ENSP00000515364.1		A0A087WYT0

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46236

AN:

151774

Hom.:

8880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.416

AC:

104317

AN:

250720

Hom.:

24916

AF XY:

0.430

AC XY:

58301

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.0973

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.361

AC:

527865

AN:

1460958

Hom.:

104814

Cov.:

AF XY:

0.371

AC XY:

269303

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0975

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.749

Gnomad4 SAS exome

AF:

0.617

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.304

AC:

46249

AN:

151892

Hom.:

8883

Cov.:

AF XY:

0.315

AC XY:

23340

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.736

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.360

Hom.:

24451

Bravo

AF:

0.301

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.318

AC:

1227

ESP6500AA

AF:

0.100

AC:

441

ESP6500EA

AF:

0.350

AC:

3013

ExAC

AF:

0.411

AC:

49919

Asia WGS

AF:

0.609

AC:

2112

AN:

3478

EpiCase

AF:

0.366

EpiControl

AF:

0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.016

DANN

Benign

0.52

DEOGEN2

Benign

0.0095

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0051

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.0080

Sift

Benign

0.26

Sift4G

Benign

0.30

Polyphen

0.011

Vest4

0.0080

MutPred

0.37

Gain of catalytic residue at H143 (P = 0);

MPC

0.024

ClinPred

0.012

GERP RS

-4.8

Varity_R

0.098

gMVP

0.032

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over