rs1177718424

Variant names:

• chr12-10809727-G-T
• rs1177718424
• NM_023917.2:c.349C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-10809727-G-T
• chr12-10809727-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_023917.2(TAS2R9):​c.349C>A​(p.Pro117Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TAS2R9 NM_023917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.349C>A	p.Pro117Thr	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.349C>A	p.Pro117Thr	missense	Exon 1 of 1	ENSP00000240691.2	Q9NYW1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151994 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250372 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461382 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.0000224 AC: 1 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151994 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74216

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.000131 AC: 2 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.026	N
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.13
Sift	Benign	0.25	T
Sift4G	Benign	0.092	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.79		Gain of MoRF binding (P = 0.0365)
MVP		0.11
MPC		0.051
ClinPred		0.78	D
GERP RS		-1.0
PromoterAI		-0.00050	Neutral
Varity_R		0.13
gMVP		0.058
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1177718424; hg19: chr12-10962326;