12-10997121-A-G

Position:

chr12-10997121-A-G

Variant summary

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

The NM_176889.4(TAS2R20):c.755T>C(p.Phe252Ser) 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 1,613,084 control chromosomes in the GnomAD database, including 113,665 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.30 ( 8852 hom., cov: 32)

Exomes 𝑓: 0.36 ( 104813 hom. )

Consequence

TAS2R20
NM_176889.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.23

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:

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=1.8801835E-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
TAS2R20	NM_176889.4 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	1/1	ENST00000538986.2	NP_795370.2
PRH1-TAS2R14	NM_001316893.2 linkuse as main transcript	c.141-23400T>C		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.478-23400T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	1/1		NM_176889.4	ENSP00000441624	P1
	ENST00000703543.1 linkuse as main transcript	c.-125-23400T>C		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46182

AN:

151858

Hom.:

8848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.416

AC:

104425

AN:

251004

Hom.:

24946

AF XY:

0.430

AC XY:

58359

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.0974

Gnomad AMR exome

AF:

0.452

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:

0.403

GnomAD4 exome

AF:

0.361

AC:

527938

AN:

1461108

Hom.:

104813

Cov.:

AF XY:

0.371

AC XY:

269340

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.0976

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:

46197

AN:

151976

Hom.:

8852

Cov.:

AF XY:

0.314

AC XY:

23304

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.735

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.352

Hom.:

15410

Bravo

AF:

0.301

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.317

AC:

1220

ESP6500AA

AF:

0.100

AC:

442

ESP6500EA

AF:

0.351

AC:

3016

ExAC

AF:

0.411

AC:

49914

Asia WGS

AF:

0.609

AC:

2110

AN:

3476

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

0.078

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.16

DANN

Benign

0.33

DEOGEN2

Benign

0.00049

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00064

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.46

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.090

REVEL

Benign

0.0010

Sift

Benign

0.40

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.012

MPC

0.030

ClinPred

0.0049

GERP RS

-2.3

Varity_R

0.056

gMVP

0.043

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