12-10997434-G-T

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.442C>A(p.His148Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,336 control chromosomes in the GnomAD database, including 113,912 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H148P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.31 ( 8996 hom., cov: 32)

Exomes 𝑓: 0.36 ( 104916 hom. )

Consequence

TAS2R20
NM_176889.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.172

Publications

47 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=3.1288212E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R20	NM_176889.4 link	c.442C>A	p.His148Asn	missense_variant	Exon 1 of 1	ENST00000538986.2	NP_795370.2	P59543

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2 link	c.442C>A	p.His148Asn	missense_variant	Exon 1 of 1	6	NM_176889.4	ENSP00000441624.1		P59543
ENSG00000275778	ENST00000536668.2 link	n.110-23713C>A		intron_variant	Intron 3 of 9	5		ENSP00000482961.1		A0A087WZY1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46963

AN:

151908

Hom.:

8993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.417

AC:

104703

AN:

250858

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.362

AC:

528688

AN:

1461310

Hom.:

104916

Cov.:

AF XY:

0.371

AC XY:

269636

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.114

AC:

3821

AN:

33476

American (AMR)

AF:

0.447

AC:

19973

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

13783

AN:

26128

East Asian (EAS)

AF:

0.748

AC:

29703

AN:

39688

South Asian (SAS)

AF:

0.617

AC:

53193

AN:

86248

European-Finnish (FIN)

AF:

0.324

AC:

17313

AN:

53390

Middle Eastern (MID)

AF:

0.555

AC:

3202

AN:

5766

European-Non Finnish (NFE)

AF:

0.328

AC:

364331

AN:

1111546

Other (OTH)

AF:

0.387

AC:

23369

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

19500

38999

58499

77998

97498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11916

23832

35748

47664

59580

<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:

0.309

AC:

46974

AN:

152026

Hom.:

8996

Cov.:

AF XY:

0.319

AC XY:

23669

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.122

AC:

5048

AN:

41528

American (AMR)

AF:

0.395

AC:

6021

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1833

AN:

3470

East Asian (EAS)

AF:

0.736

AC:

3798

AN:

5160

South Asian (SAS)

AF:

0.621

AC:

2985

AN:

4806

European-Finnish (FIN)

AF:

0.330

AC:

3479

AN:

10558

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22672

AN:

67938

Other (OTH)

AF:

0.365

AC:

772

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1462

2924

4386

5848

7310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.343

Hom.:

41456

Bravo

AF:

0.306

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.318

AC:

1227

ESP6500AA

AF:

0.119

AC:

524

ESP6500EA

AF:

0.350

AC:

3014

ExAC

AF:

0.413

AC:

50126

Asia WGS

AF:

0.609

AC:

2113

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

0.056

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.046

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.00039

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00014

MetaRNN

Benign

0.0000031

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-2.6

PhyloP100

-0.17

PrimateAI

Benign

0.29

PROVEAN

Benign

3.0

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MPC

0.024

ClinPred

0.010

GERP RS

0.52

Varity_R

0.038

gMVP

0.024

Mutation Taster

=95/5

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