12-10997170-T-C

Variant names:

• chr12-10997170-T-C
• rs10845281
• NM_176889.4:c.706A>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.706A>G​(p.Ile236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,804 control chromosomes in the GnomAD database, including 113,751 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 0.30 (8925 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104826 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 34 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=1.1594881E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R20	NM_176889.4	MANE Select	c.706A>G	p.Ile236Val	missense	Exon 1 of 1	NP_795370.2
	PRH1	NM_001291315.2		c.37-23449A>G		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-23449A>G		intron	N/A	NP_001278243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R20	ENST00000538986.2	TSL:6 MANE Select	c.706A>G	p.Ile236Val	missense	Exon 1 of 1	ENSP00000441624.1
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-23449A>G		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-125-23449A>G		intron	N/A	ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46333 AN: 151992 Hom.: 8922 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.416 AC: 104511 AN: 251092 AF XY: 0.430

Gnomad AFR exome AF: 0.0976

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.361 AC: 528251 AN: 1461694 Hom.: 104826 Cov.: 50 AF XY: 0.371 AC XY: 269483 AN XY: 727136

African (AFR) AF: 0.0978 AC: 3274 AN: 33472

American (AMR) AF: 0.446 AC: 19958 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13784 AN: 26130

East Asian (EAS) AF: 0.749 AC: 29715 AN: 39696

South Asian (SAS) AF: 0.617 AC: 53189 AN: 86250

European-Finnish (FIN) AF: 0.324 AC: 17318 AN: 53412

Middle Eastern (MID) AF: 0.554 AC: 3196 AN: 5764

European-Non Finnish (NFE) AF: 0.328 AC: 364499 AN: 1111878

Other (OTH) AF: 0.386 AC: 23318 AN: 60384

GnomAD4 genome AF: 0.305 AC: 46346 AN: 152110 Hom.: 8925 Cov.: 32 AF XY: 0.315 AC XY: 23394 AN XY: 74338

African (AFR) AF: 0.106 AC: 4411 AN: 41524

American (AMR) AF: 0.394 AC: 6013 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1833 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3792 AN: 5150

South Asian (SAS) AF: 0.621 AC: 2995 AN: 4822

European-Finnish (FIN) AF: 0.329 AC: 3477 AN: 10572

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22689 AN: 67986

Other (OTH) AF: 0.363 AC: 768 AN: 2114

Alfa AF: 0.349 Hom.: 19580

Bravo AF: 0.301

TwinsUK AF: 0.321 AC: 1191

ALSPAC AF: 0.321 AC: 1238

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.351 AC: 3016

ExAC AF: 0.411 AC: 49945

Asia WGS AF: 0.609 AC: 2112 AN: 3478

EpiCase AF: 0.366

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.34
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0073	N
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PhyloP100		-0.60
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.042
Sift	Benign	0.057	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.015
MPC		0.022
ClinPred		0.0041	T
GERP RS		-1.6
Varity_R		0.061
gMVP		0.017
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10845281; hg19: chr12-11149769; COSMIC: COSV67856042;