12-10809626-A-T

Position:

• chr12-10809626-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.598

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]

ACMG classification

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/exons	MANE	Protein	UniProt
TAS2R9	NM_023917.2	c.450T>A	p.Asp150Glu	missense_variant	1/1	ENST00000240691.4	NP_076406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R9	ENST00000240691.4	c.450T>A	p.Asp150Glu	missense_variant	1/1		NM_023917.2	ENSP00000240691	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1759 AN: 151942 Hom.: 33 Cov.: 32

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.: 10 AF XY: 0.00219 AC XY: 296 AN XY: 135208

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.: 39 Cov.: 33 AF XY: 0.00110 AC XY: 800 AN XY: 727042

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.: 34 Cov.: 32 AF XY: 0.0113 AC XY: 837 AN XY: 74348

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.: 3

Bravo AF: 0.0131

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0365 AC: 161

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00332 AC: 403

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.025
DANN	Benign	0.58
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.033	N
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.26	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.034
Sift	Benign	0.97	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.026
MutPred		0.46		Gain of ubiquitination at K148 (P = 0.1008);
MVP		0.25
MPC		0.0087
ClinPred		0.0015	T
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

Other links and lift over

dbSNP: rs74954631; hg19: chr12-10962225; COSMIC: COSV99078544; COSMIC: COSV99078544;