NM_023917.2:c.419T>A

Variant names:

• chr12-10809657-A-T
• rs1391709062
• NM_023917.2:c.419T>A

Variant summary

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

The NM_023917.2(TAS2R9):​c.419T>A​(p.Ile140Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,056 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I140T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TAS2R9 NM_023917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• 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.419T>A	p.Ile140Asn	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.419T>A	p.Ile140Asn	missense	Exon 1 of 1	ENSP00000240691.2	Q9NYW1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0022	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.064
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.046
Sift	Benign	0.068	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
Vest4		0.42
MutPred		0.77		Loss of stability (P = 0.0119)
MVP		0.099
MPC		0.0094
ClinPred		0.90	D
GERP RS		1.3
Varity_R		0.24
gMVP		0.17
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: rs1391709062; hg19: chr12-10962256;