rs10772420

Positions:

chr12-11021677-G-A

Variant summary

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

The NM_176888.2(TAS2R19):c.895C>T(p.Arg299Cys) 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 1,358,012 control chromosomes in the GnomAD database, including 181,501 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.56 ( 16550 hom., cov: 48)

Exomes 𝑓: 0.53 ( 181501 hom. )

Failed GnomAD Quality Control

Consequence

TAS2R19
NM_176888.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Variant links:

Genes affected

TAS2R19 (HGNC:19108): (taste 2 receptor member 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of taste. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TAS2R19 links:

PRH1-TAS2R14 (HGNC:):

PRH1-TAS2R14 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8176775E-4).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAS2R19	NM_176888.2 linkuse as main transcript	c.895C>T	p.Arg299Cys	missense_variant	1/1	ENST00000390673.2	NP_795369.1
PRH1-TAS2R14	NM_001316893.2 linkuse as main transcript	c.140+13105C>T		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.477+13105C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R19	ENST00000390673.2 linkuse as main transcript	c.895C>T	p.Arg299Cys	missense_variant	1/1		NM_176888.2	ENSP00000375091	P1
	ENST00000703543.1 linkuse as main transcript	c.-126+25343C>T		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

83208

AN:

148308

Hom.:

16551

Cov.:

FAILED QC

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.679

Gnomad MID

AF:

0.530

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.450

AC:

110094

AN:

244806

Hom.:

26022

AF XY:

0.444

AC XY:

58765

AN XY:

132380

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.604

Gnomad NFE exome

AF:

0.522

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.533

AC:

723948

AN:

1358012

Hom.:

181501

Cov.:

AF XY:

0.532

AC XY:

355172

AN XY:

668102

show subpopulations

Gnomad4 AFR exome

AF:

0.375

Gnomad4 AMR exome

AF:

0.519

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.675

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.508

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.561

AC:

83219

AN:

148418

Hom.:

16550

Cov.:

AF XY:

0.563

AC XY:

40839

AN XY:

72486

show subpopulations

Gnomad4 AFR

AF:

0.417

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.679

Gnomad4 NFE

AF:

0.627

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.487

Hom.:

36551

TwinsUK

AF:

0.532

AC:

1973

ALSPAC

AF:

0.533

AC:

2053

ESP6500AA

AF:

0.379

AC:

1670

ESP6500EA

AF:

0.501

AC:

4311

ExAC

AF:

0.455

AC:

55212

Asia WGS

AF:

0.299

AC:

1042

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00020

MetaRNN

Benign

0.00038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

2.9

REVEL

Benign

0.029

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.036

MPC

0.016

ClinPred

0.021

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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