12-11092122-G-C

Position:

chr12-11092122-G-C

Variant summary

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

The NM_176884.2(TAS2R43):c.108C>G(p.Phe36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 874,090 control chromosomes in the GnomAD database, including 121,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 4887 hom., cov: 22)

Exomes 𝑓: 0.51 ( 116233 hom. )

Consequence

TAS2R43
NM_176884.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.131

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=0.002693683).

BP6

Variant 12-11092122-G-C is Benign according to our data. Variant chr12-11092122-G-C is described in ClinVar as [Benign]. Clinvar id is 768522.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 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.108C>G	p.Phe36Leu	missense_variant	1/1	ENST00000531678.1	NP_795365.2
PRH1-TAS2R14	NM_001316893.2 linkuse as main transcript	c.-133-44934C>G		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.205-44934C>G		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.108C>G	p.Phe36Leu	missense_variant	1/1		NM_176884.2	ENSP00000431719	P1
TAS2R14	ENST00000381852.4 linkuse as main transcript	n.153-44934C>G		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5 linkuse as main transcript	n.124-44934C>G		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1 linkuse as main transcript	n.358+28888C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

38770

AN:

91448

Hom.:

4885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.00274

AC:

531

AN:

194040

Hom.:

197

AF XY:

0.00234

AC XY:

249

AN XY:

106340

show subpopulations

Gnomad AFR exome

AF:

0.000680

Gnomad AMR exome

AF:

0.000943

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.000233

Gnomad SAS exome

AF:

0.0000709

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.00355

GnomAD4 exome

AF:

0.512

AC:

400849

AN:

782526

Hom.:

116233

Cov.:

AF XY:

0.513

AC XY:

199926

AN XY:

389728

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.506

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.502

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.689

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.424

AC:

38782

AN:

91564

Hom.:

4887

Cov.:

AF XY:

0.426

AC XY:

18973

AN XY:

44528

show subpopulations

Gnomad4 AFR

AF:

0.240

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.514

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.524

Hom.:

1806

ExAC

AF:

0.0429

AC:

4474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

0.24

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

1.9

REVEL

Benign

0.078

Sift

Benign

0.036

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.053

MutPred

0.47

Loss of methylation at K37 (P = 0.0386);

MPC

0.12

ClinPred

0.0038

GERP RS

2.0

Varity_R

0.072

gMVP

0.044

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

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