rs7135018

Variant names:

• chr12-10997641-T-C
• rs7135018
• NM_176889.4:c.235A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 39 publications found

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]

ENSG00000275778 (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]

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.235A>G	p.Lys79Glu	missense_variant	Exon 1 of 1	ENST00000538986.2	NP_795370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2	c.235A>G	p.Lys79Glu	missense_variant	Exon 1 of 1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000536668.2	n.110-23920A>G		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

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

GnomAD2 exomes AF: 0.227 AC: 56455 AN: 249032 AF XY: 0.224

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 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

African (AFR) AF: 0.204 AC: 6823 AN: 33476

American (AMR) AF: 0.239 AC: 10676 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4374 AN: 26118

East Asian (EAS) AF: 0.224 AC: 8878 AN: 39674

South Asian (SAS) AF: 0.186 AC: 15990 AN: 86144

European-Finnish (FIN) AF: 0.272 AC: 14525 AN: 53394

Middle Eastern (MID) AF: 0.171 AC: 981 AN: 5740

European-Non Finnish (NFE) AF: 0.240 AC: 266532 AN: 1111776

Other (OTH) AF: 0.227 AC: 13703 AN: 60366

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

African (AFR) AF: 0.202 AC: 8376 AN: 41508

American (AMR) AF: 0.217 AC: 3313 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5164

South Asian (SAS) AF: 0.188 AC: 905 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2920 AN: 10598

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16155 AN: 67986

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.226 Hom.: 9389

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
PhyloP100		-2.5
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
Mutation Taster		=100/0	polymorphism (auto)

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