12-10997121-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.30 ( 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

Publications

30 publications found

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:

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

PRR4 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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAS2R20	NM_176889.4 link	c.755T>C	p.Phe252Ser	missense_variant	Exon 1 of 1	ENST00000538986.2	NP_795370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2 link	c.755T>C	p.Phe252Ser	missense_variant	Exon 1 of 1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000536668.2 link	n.110-23400T>C		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

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

GnomAD2 exomes

AF:

0.416

AC:

104425

AN:

251004

AF XY:

0.430

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 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

African (AFR)

AF:

0.0976

AC:

3267

AN:

33472

American (AMR)

AF:

0.446

AC:

19954

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

13784

AN:

26130

East Asian (EAS)

AF:

0.749

AC:

29709

AN:

39690

South Asian (SAS)

AF:

0.617

AC:

53167

AN:

86210

European-Finnish (FIN)

AF:

0.324

AC:

17318

AN:

53414

Middle Eastern (MID)

AF:

0.555

AC:

3197

AN:

5764

European-Non Finnish (NFE)

AF:

0.328

AC:

364232

AN:

1111356

Other (OTH)

AF:

0.386

AC:

23310

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

18528

37056

55585

74113

92641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11906

23812

35718

47624

59530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.304

AC:

46197

AN:

151976

Hom.:

8852

Cov.:

AF XY:

0.314

AC XY:

23304

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.106

AC:

4406

AN:

41532

American (AMR)

AF:

0.392

AC:

5982

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1833

AN:

3470

East Asian (EAS)

AF:

0.735

AC:

3773

AN:

5132

South Asian (SAS)

AF:

0.621

AC:

2989

AN:

4812

European-Finnish (FIN)

AF:

0.327

AC:

3440

AN:

10534

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22639

AN:

67934

Other (OTH)

AF:

0.363

AC:

767

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1503

3007

4510

6014

7517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.344

Hom.:

21688

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

(source)

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

PhyloP100

-3.2

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.090

REVEL

Benign

0.0010

Sift

Benign

0.40

Sift4G

Benign

0.40

Vest4

0.012

ClinPred

0.0049

GERP RS

-2.3

Varity_R

0.056

gMVP

0.043

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over