rs10845279

Variant names:

• chr12-10997112-C-A
• rs10845279
• NM_176889.4:c.764G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-10997112-C-A
• chr12-10997112-C-G
• chr12-10997112-C-T

Variant summary

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

The NM_176889.4(TAS2R20):​c.764G>T​(p.Arg255Leu) 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 1,612,704 control chromosomes in the GnomAD database, including 113,653 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 (8846 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104807 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 41 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=5.843094E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R20	NM_176889.4	MANE Select	c.764G>T	p.Arg255Leu	missense	Exon 1 of 1	NP_795370.2	P59543
	PRH1	NM_001291315.2		c.37-23391G>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-23391G>T		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R20	ENST00000538986.2	TSL:6 MANE Select	c.764G>T	p.Arg255Leu	missense	Exon 1 of 1	ENSP00000441624.1	P59543
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-23391G>T		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-125-23391G>T		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46162 AN: 151686 Hom.: 8842 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.416 AC: 104409 AN: 250982 AF XY: 0.430

Gnomad AFR exome AF: 0.0975

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.751

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.361 AC: 527836 AN: 1460898 Hom.: 104807 Cov.: 48 AF XY: 0.371 AC XY: 269302 AN XY: 726798

African (AFR) AF: 0.0976 AC: 3266 AN: 33470

American (AMR) AF: 0.446 AC: 19950 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13783 AN: 26128

East Asian (EAS) AF: 0.749 AC: 29707 AN: 39688

South Asian (SAS) AF: 0.617 AC: 53168 AN: 86208

European-Finnish (FIN) AF: 0.324 AC: 17315 AN: 53412

Middle Eastern (MID) AF: 0.555 AC: 3198 AN: 5764

European-Non Finnish (NFE) AF: 0.328 AC: 364145 AN: 1111182

Other (OTH) AF: 0.386 AC: 23304 AN: 60354

GnomAD4 genome AF: 0.304 AC: 46177 AN: 151806 Hom.: 8846 Cov.: 32 AF XY: 0.314 AC XY: 23292 AN XY: 74162

African (AFR) AF: 0.106 AC: 4404 AN: 41472

American (AMR) AF: 0.393 AC: 5986 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1830 AN: 3468

East Asian (EAS) AF: 0.735 AC: 3767 AN: 5126

South Asian (SAS) AF: 0.622 AC: 2988 AN: 4806

European-Finnish (FIN) AF: 0.328 AC: 3442 AN: 10504

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

European-Non Finnish (NFE) AF: 0.333 AC: 22627 AN: 67888

Other (OTH) AF: 0.364 AC: 767 AN: 2110

Alfa AF: 0.354 Hom.: 34730

Bravo AF: 0.301

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.317 AC: 1220

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.351 AC: 3016

ExAC AF: 0.411 AC: 49914

Asia WGS AF: 0.608 AC: 2109 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	0.093
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0030
DANN	Benign	0.41
DEOGEN2	Benign	0.00025	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00072	N
MetaRNN	Benign	0.0000058	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.2	N
PhyloP100		-0.89
PrimateAI	Benign	0.23	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.047
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.025
ClinPred		0.0031	T
GERP RS		-5.3
Varity_R		0.047
gMVP		0.034
Mutation Taster		=100/0	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: rs10845279; hg19: chr12-11149711; COSMIC: COSV67856037;