12-11091769-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_176884.2(TAS2R43):c.461G>A(p.Arg154Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,358,928 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 3 hom., cov: 22)

Exomes 𝑓: 0.000051 ( 10 hom. )

Consequence

TAS2R43
NM_176884.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.67

Publications

2 publications found

Variant links:

Genes affected

TAS2R43 (HGNC:18875): (taste 2 receptor member 43) TAS2R43 belongs to the large TAS2R receptor family. TAS2Rs are expressed on the surface of taste receptor cells and mediate the perception of bitterness through a G protein-coupled second messenger pathway (Conte et al., 2002 [PubMed 12584440]). For further information on TAS2Rs, see MIM 604791.[supplied by OMIM, Mar 2009]

TAS2R43 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012465537).

BP6

Variant 12-11091769-C-T is Benign according to our data. Variant chr12-11091769-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2213629.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176884.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAS2R43	NM_176884.2	MANE Select	c.461G>A	p.Arg154Gln	missense	Exon 1 of 1	NP_795365.2	P59537
PRH1	NM_001291315.2		c.-133-44581G>A		intron	N/A	NP_001278244.1
PRH1	NM_001291314.2		c.-294-44581G>A		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAS2R43	ENST00000531678.1	TSL:6 MANE Select	c.461G>A	p.Arg154Gln	missense	Exon 1 of 1	ENSP00000431719.1	P59537
ENSG00000275778	ENST00000536668.2	TSL:5	n.-164-44581G>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
PRR4	ENST00000535024.7	TSL:5	c.-133-44581G>A		intron	N/A	ENSP00000481571.3	A0A087WY73

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

126598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000185

Gnomad OTH

AF:

0.00172

GnomAD2 exomes

AF:

0.0000900

AC:

AN:

199932

AF XY:

0.0000733

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1232330

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

620642

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

31198

American (AMR)

AF:

0.0000714

AC:

AN:

42046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25126

East Asian (EAS)

AF:

0.00

AC:

AN:

39356

South Asian (SAS)

AF:

0.0000597

AC:

AN:

83760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00000887

AC:

AN:

901644

Other (OTH)

AF:

0.000186

AC:

AN:

53798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.597

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000237

AC:

AN:

126598

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

AN XY:

61584

show subpopulations

African (AFR)

AF:

0.000546

AC:

AN:

36600

American (AMR)

AF:

0.000471

AC:

AN:

12728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3210

East Asian (EAS)

AF:

0.00

AC:

AN:

4962

South Asian (SAS)

AF:

0.00

AC:

AN:

4462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

54092

Other (OTH)

AF:

0.00172

AC:

AN:

1748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000826

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000970

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0090

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00040

LIST_S2

Benign

0.68

M_CAP

Benign

0.0018

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-3.7

PrimateAI

Benign

0.22

PROVEAN

Benign

1.8

REVEL

Benign

0.0090

Sift

Benign

0.49

Sift4G

Benign

0.71

Polyphen

0.0030

Vest4

0.041

MVP

0.17

MPC

0.12

ClinPred

0.0084

GERP RS

-4.0

Varity_R

0.022

gMVP

0.033

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over