12-10809423-C-T

Position:

• chr12-10809423-C-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.653G>A​(p.Gly218Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00525 in 1,613,382 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0049 (82 hom.)
• Consequence: TAS2R9 NM_023917.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.514

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=0.004649937).
• BP6: Variant 12-10809423-C-T is Benign according to our data. Variant chr12-10809423-C-T is described in ClinVar as [Benign]. Clinvar id is 786420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00829 (1258/151836) while in subpopulation SAS AF= 0.0278 (134/4820). AF 95% confidence interval is 0.024. There are 12 homozygotes in gnomad4. There are 652 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R9	NM_023917.2	c.653G>A	p.Gly218Glu	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.653G>A	p.Gly218Glu	missense_variant	1/1	6	NM_023917.2	ENSP00000240691.2

Frequencies

GnomAD3 genomes AF: 0.00826 AC: 1253 AN: 151718 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00605

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00863

GnomAD3 exomes AF: 0.00732 AC: 1835 AN: 250648 Hom.: 21 AF XY: 0.00840 AC XY: 1138 AN XY: 135450

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0265

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00802

GnomAD4 exome AF: 0.00494 AC: 7214 AN: 1461546 Hom.: 82 Cov.: 30 AF XY: 0.00576 AC XY: 4186 AN XY: 727058

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.00394

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0282

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00262

Gnomad4 OTH exome AF: 0.00638

GnomAD4 genome AF: 0.00829 AC: 1258 AN: 151836 Hom.: 12 Cov.: 31 AF XY: 0.00879 AC XY: 652 AN XY: 74192

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.00604

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00464 Hom.: 6

Bravo AF: 0.00830

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00814 AC: 988

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00480

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	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.17	N
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.047
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.28
MVP		0.085
MPC		0.032
ClinPred		0.082	T
GERP RS		1.6
Varity_R		0.39
gMVP		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs113883583; hg19: chr12-10962022;