12-10809875-G-T

Variant names:

• chr12-10809875-G-T
• rs61735347
• NM_023917.2:c.201C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_023917.2(TAS2R9):​c.201C>A​(p.Phe67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,613,792 control chromosomes in the GnomAD database, including 11 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 0.0047 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: TAS2R9 NM_023917.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034289062).
• BP6: Variant 12-10809875-G-T is Benign according to our data. Variant chr12-10809875-G-T is described in ClinVar as Benign. ClinVar VariationId is 789806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00467 (711/152202) while in subpopulation AFR AF = 0.0163 (679/41548). AF 95% confidence interval is 0.0153. There are 5 homozygotes in GnomAd4. There are 331 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.201C>A	p.Phe67Leu	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.201C>A	p.Phe67Leu	missense	Exon 1 of 1	ENSP00000240691.2	Q9NYW1

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152084 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00119 AC: 299 AN: 250520 AF XY: 0.000857

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000407 AC: 595 AN: 1461590 Hom.: 6 Cov.: 33 AF XY: 0.000338 AC XY: 246 AN XY: 727104

African (AFR) AF: 0.0152 AC: 508 AN: 33464

American (AMR) AF: 0.000762 AC: 34 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111874

Other (OTH) AF: 0.000778 AC: 47 AN: 60382

GnomAD4 genome AF: 0.00467 AC: 711 AN: 152202 Hom.: 5 Cov.: 32 AF XY: 0.00445 AC XY: 331 AN XY: 74414

African (AFR) AF: 0.0163 AC: 679 AN: 41548

American (AMR) AF: 0.00177 AC: 27 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00183 Hom.: 3

Bravo AF: 0.00510

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00149 AC: 181

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.8
DANN	Benign	0.85
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.99	L
PhyloP100		-0.11
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.035
Sift	Benign	0.27	T
Sift4G	Benign	0.33	T
Polyphen		0.016	B
Vest4		0.025
MutPred		0.59		Gain of helix (P = 0.132)
MVP		0.014
MPC		0.0083
ClinPred		0.0015	T
GERP RS		-1.3
PromoterAI		-0.013	Neutral
Varity_R		0.12
gMVP		0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61735347; hg19: chr12-10962474;