chr12-10809423-C-T

Variant names:

• chr12-10809423-C-T
• rs113883583
• NM_023917.2:c.653G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R9	NM_023917.2	MANE Select	c.653G>A	p.Gly218Glu	missense	Exon 1 of 1	NP_076406.1	Q9NYW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R9	ENST00000240691.4	TSL:6 MANE Select	c.653G>A	p.Gly218Glu	missense	Exon 1 of 1	ENSP00000240691.2	Q9NYW1

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

GnomAD2 exomes AF: 0.00732 AC: 1835 AN: 250648 AF XY: 0.00840

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 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

African (AFR) AF: 0.0201 AC: 671 AN: 33458

American (AMR) AF: 0.00394 AC: 176 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 482 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0282 AC: 2434 AN: 86254

European-Finnish (FIN) AF: 0.000524 AC: 28 AN: 53396

Middle Eastern (MID) AF: 0.0205 AC: 118 AN: 5760

European-Non Finnish (NFE) AF: 0.00262 AC: 2918 AN: 1111856

Other (OTH) AF: 0.00638 AC: 385 AN: 60382

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

African (AFR) AF: 0.0187 AC: 772 AN: 41386

American (AMR) AF: 0.00604 AC: 92 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4820

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10562

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 174 AN: 67932

Other (OTH) AF: 0.00854 AC: 18 AN: 2108

Alfa AF: 0.00567 Hom.: 13

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.51
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs113883583; hg19: chr12-10962022;