7-122994970-C-T

Variant names:

• chr7-122994970-C-T
• rs860170
• NM_016945.3:c.665G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_016945.3(TAS2R16):​c.665G>A​(p.Arg222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,613,532 control chromosomes in the GnomAD database, including 382,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.74 (42587 hom., cov: 31)
  • Exomes 𝑓: 0.68 (339726 hom.)
• Consequence: TAS2R16 NM_016945.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.56

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3664874E-6).
• BP6: Variant 7-122994970-C-T is Benign according to our data. Variant chr7-122994970-C-T is described in ClinVar as [Benign]. Clinvar id is 3058839.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R16	NM_016945.3	c.665G>A	p.Arg222His	missense_variant	Exon 1 of 1	ENST00000249284.3	NP_058641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R16	ENST00000249284.3	c.665G>A	p.Arg222His	missense_variant	Exon 1 of 1	6	NM_016945.3	ENSP00000249284.2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112275 AN: 151852 Hom.: 42517 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.736

GnomAD3 exomes AF: 0.684 AC: 171207 AN: 250376 Hom.: 59369 AF XY: 0.681 AC XY: 92164 AN XY: 135284

Gnomad AFR exome AF: 0.913

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.532

Gnomad SAS exome AF: 0.691

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.682

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.680 AC: 993779 AN: 1461560 Hom.: 339726 Cov.: 70 AF XY: 0.680 AC XY: 494303 AN XY: 727092

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.740 AC: 112408 AN: 151972 Hom.: 42587 Cov.: 31 AF XY: 0.737 AC XY: 54723 AN XY: 74246

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.740

Alfa AF: 0.686 Hom.: 87921

Bravo AF: 0.755

TwinsUK AF: 0.688 AC: 2551

ALSPAC AF: 0.693 AC: 2672

ESP6500AA AF: 0.904 AC: 3984

ESP6500EA AF: 0.677 AC: 5822

ExAC AF: 0.688 AC: 83485

Asia WGS AF: 0.678 AC: 2356 AN: 3478

EpiCase AF: 0.677

EpiControl AF: 0.675

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TAS2R16-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.049
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.8	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	7.2	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.011
ClinPred		0.0019	T
GERP RS		2.2
Varity_R		0.030
gMVP		0.089

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

Publications

LitVar

Other links and lift over

dbSNP: rs860170; hg19: chr7-122635024; COSMIC: COSV50798563;