Genetic Variant TAS2R9:p.Asp150Glu (chr12-10809626-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_023917.2(TAS2R9):c.450T>A(p.Asp150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,564 control chromosomes in the GnomAD database, including 73 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 0.012 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 39 hom. )

Consequence

TAS2R9
NM_023917.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.598

Variant links:

Genes affected

TAS2R9 (HGNC:14917): (taste 2 receptor member 9) 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]

TAS2R9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032548904).

BP6

Variant 12-10809626-A-T is Benign according to our data. Variant chr12-10809626-A-T is described in ClinVar as [Benign]. Clinvar id is 784233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1761/152050) while in subpopulation AFR AF= 0.0401 (1658/41396). AF 95% confidence interval is 0.0384. There are 34 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R9	NM_023917.2 link	c.450T>A	p.Asp150Glu	missense_variant	Exon 1 of 1	ENST00000240691.4	NP_076406.1	Q9NYW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R9	ENST00000240691.4 link	c.450T>A	p.Asp150Glu	missense_variant	Exon 1 of 1	6	NM_023917.2	ENSP00000240691.2		Q9NYW1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1759

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00407

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00284

AC:

709

AN:

250048

Hom.:

AF XY:

0.00219

AC XY:

296

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00124

AC:

1810

AN:

1461514

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

800

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000764

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.0116

AC:

1761

AN:

152050

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

837

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0401

Gnomad4 AMR

AF:

0.00400

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0365

AC:

161

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00332

AC:

403

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.025

DANN

Benign

0.58

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.033

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.26

PrimateAI

Benign

0.23

PROVEAN

Benign

0.030

REVEL

Benign

0.034

Sift

Benign

0.97

Sift4G

Benign

0.29

Polyphen

0.0040

Vest4

0.026

MutPred

0.46

Gain of ubiquitination at K148 (P = 0.1008);

MVP

0.25

MPC

0.0087

ClinPred

0.0015

GERP RS

-5.2

Varity_R

0.032

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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