12-11092132-A-G

Position:

chr12-11092132-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_176884.2(TAS2R43):c.98T>C(p.Ile33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 787,018 control chromosomes in the GnomAD database, including 100,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.38 ( 3074 hom., cov: 22)

Exomes 𝑓: 0.45 ( 97080 hom. )

Consequence

TAS2R43
NM_176884.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.18

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:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.146299E-4).

BP6

Variant 12-11092132-A-G is Benign according to our data. Variant chr12-11092132-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 768525.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAS2R43	NM_176884.2 linkuse as main transcript	c.98T>C	p.Ile33Thr	missense_variant	1/1	ENST00000531678.1	NP_795365.2
PRH1-TAS2R14	NM_001316893.2 linkuse as main transcript	c.-133-44944T>C		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.205-44944T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TAS2R43	ENST00000531678.1 linkuse as main transcript	c.98T>C	p.Ile33Thr	missense_variant	1/1		NM_176884.2	ENSP00000431719	P1
TAS2R14	ENST00000381852.4 linkuse as main transcript	n.153-44944T>C		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5 linkuse as main transcript	n.124-44944T>C		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1 linkuse as main transcript	n.358+28878T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

31056

AN:

81916

Hom.:

3072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.381

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.380

GnomAD3 exomes

AF:

0.00171

AC:

336

AN:

196906

Hom.:

116

AF XY:

0.00161

AC XY:

174

AN XY:

107910

show subpopulations

Gnomad AFR exome

AF:

0.000449

Gnomad AMR exome

AF:

0.000681

Gnomad ASJ exome

AF:

0.000557

Gnomad EAS exome

AF:

0.000403

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00552

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.455

AC:

320658

AN:

704966

Hom.:

97080

Cov.:

AF XY:

0.458

AC XY:

160856

AN XY:

351524

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.476

Gnomad4 SAS exome

AF:

0.326

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.442

GnomAD4 genome

AF:

0.379

AC:

31071

AN:

82052

Hom.:

3074

Cov.:

AF XY:

0.383

AC XY:

15275

AN XY:

39892

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.441

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.445

Hom.:

1907

ESP6500AA

AF:

0.0123

AC:

ESP6500EA

AF:

0.0315

AC:

219

ExAC

AF:

0.0389

AC:

4043

Asia WGS

AF:

0.000317

AC:

AN:

3170

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0060

DANN

Benign

0.61

DEOGEN2

Benign

0.013

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.46

MetaRNN

Benign

0.00071

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.99

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.043

Sift

Benign

0.29

Sift4G

Benign

0.25

Polyphen

0.0030

Vest4

0.073

MPC

0.14

ClinPred

0.0068

GERP RS

2.0

Varity_R

0.054

gMVP

0.051

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over