rs7135018

Positions:

• chr12-10997641-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176889.4(TAS2R20):​c.235A>G​(p.Lys79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,478 control chromosomes in the GnomAD database, including 44,600 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (3842 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40758 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

Genes affected

TAS2R20 (HGNC:19109): (taste 2 receptor member 20) This gene encodes a member of the taste receptor two family of class C G-protein coupled receptors. Receptors of this family have a short extracellular N-terminus, seven transmembrane helices, three extracellular loops and three intracellular loops, and an intracellular C-terminus. Members of this family are expressed in a subset of taste receptor cells, where they function in bitter taste reception, as well as in non-gustatory cells including those of the brain, reproductive organs, respiratory system, and gastrointestinal system. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2016]

PRH1-TAS2R14 (HGNC:):

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

TAS2R14 (HGNC:14920): (taste 2 receptor member 14) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015335411).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R20	NM_176889.4	c.235A>G	p.Lys79Glu	missense_variant	1/1	ENST00000538986.2
PRH1-TAS2R14	NM_001316893.2	c.141-23920A>G		intron_variant
PRH1-PRR4	NR_037918.2	n.478-23920A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R20	ENST00000538986.2	c.235A>G	p.Lys79Glu	missense_variant	1/1		NM_176889.4	P1
	ENST00000703543.1	c.-125-23920A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33972 AN: 152016 Hom.: 3840 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.227 AC: 56455 AN: 249032 Hom.: 6554 AF XY: 0.224 AC XY: 30310 AN XY: 135148

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.234 AC: 342482 AN: 1461344 Hom.: 40758 Cov.: 53 AF XY: 0.233 AC XY: 169067 AN XY: 726942

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.223 AC: 33985 AN: 152134 Hom.: 3842 Cov.: 32 AF XY: 0.226 AC XY: 16768 AN XY: 74358

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.213

Alfa AF: 0.228 Hom.: 7519

Bravo AF: 0.217

TwinsUK AF: 0.236 AC: 876

ALSPAC AF: 0.249 AC: 959

ESP6500AA AF: 0.206 AC: 889

ESP6500EA AF: 0.228 AC: 1950

ExAC AF: 0.225 AC: 27293

Asia WGS AF: 0.241 AC: 838 AN: 3478

EpiCase AF: 0.223

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0040
DANN	Benign	0.46
DEOGEN2	Benign	0.00086	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0023	N
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.0080
MPC		0.027
ClinPred		0.00058	T
GERP RS		-4.2
Varity_R		0.048
gMVP		0.031

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: rs7135018; hg19: chr12-11150240; COSMIC: COSV67860971;