7-122995119-A-C

Variant names:

• chr7-122995119-A-C
• rs846664
• NM_016945.3:c.516T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016945.3(TAS2R16):​c.516T>G​(p.Asn172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,670 control chromosomes in the GnomAD database, including 3,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.081 (1688 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (1536 hom.)
• Consequence: TAS2R16 NM_016945.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:2
• Conservation: PhyloP100: -2.04
• Publications: 30 publications found

Genes affected

TAS2R16 (HGNC:14921): (taste 2 receptor member 16) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily. These family members are specifically expressed by taste receptor cells of the tongue and palate epithelia. Each of these apparently intronless genes encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes in chromosome 7 and is genetically linked to loci that influence bitter perception. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0087378025).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016945.3. 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
	TAS2R16	NM_016945.3	MANE Select	c.516T>G	p.Asn172Lys	missense	Exon 1 of 1	NP_058641.1	Q9NYV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R16	ENST00000249284.3	TSL:6 MANE Select	c.516T>G	p.Asn172Lys	missense	Exon 1 of 1	ENSP00000249284.2	Q9NYV7

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12296 AN: 151880 Hom.: 1682 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0559

GnomAD2 exomes AF: 0.0214 AC: 5362 AN: 250772 AF XY: 0.0157

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.0133

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000936

Gnomad OTH exome AF: 0.00999

GnomAD4 exome AF: 0.00848 AC: 12395 AN: 1461672 Hom.: 1536 Cov.: 33 AF XY: 0.00731 AC XY: 5317 AN XY: 727140

African (AFR) AF: 0.294 AC: 9843 AN: 33462

American (AMR) AF: 0.0152 AC: 680 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000626 AC: 54 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5760

European-Non Finnish (NFE) AF: 0.000616 AC: 685 AN: 1111890

Other (OTH) AF: 0.0175 AC: 1059 AN: 60382

GnomAD4 genome AF: 0.0810 AC: 12318 AN: 151998 Hom.: 1688 Cov.: 32 AF XY: 0.0772 AC XY: 5733 AN XY: 74292

African (AFR) AF: 0.283 AC: 11709 AN: 41436

American (AMR) AF: 0.0266 AC: 406 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

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

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67974

Other (OTH) AF: 0.0553 AC: 117 AN: 2114

Alfa AF: 0.0248 Hom.: 2182

Bravo AF: 0.0925

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.274 AC: 1206

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.0260 AC: 3152

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Alcohol dependence (1)
-	-	-	Alcohol dependence, susceptibility to (1)
-	-	-	BETA-GLUCOPYRANOSIDE TASTING (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.089
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.026
Sift	Benign	0.94	T
Sift4G	Benign	0.96	T
Polyphen		0.0	B
Vest4		0.026
MutPred		0.14		Gain of methylation at N172 (P = 0.0039)
MPC		0.011
ClinPred		0.0020	T
GERP RS		-3.5
Varity_R		0.038
gMVP		0.053
Mutation Taster		=99/1	polymorphism (auto)

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: rs846664; hg19: chr7-122635173; COSMIC: COSV50797006;