chr12-10997447-G-T

Variant names:

• chr12-10997447-G-T
• rs12226920
• NM_176889.4:c.429C>A

Variant summary

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

The NM_176889.4(TAS2R20):​c.429C>A​(p.His143Gln) 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 1,612,850 control chromosomes in the GnomAD database, including 113,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H143P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.30 (8883 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104814 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 43 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=2.8293484E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 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.429C>A	p.His143Gln	missense	Exon 1 of 1	NP_795370.2
	PRH1	NM_001291315.2		c.37-23726C>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-23726C>A		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.429C>A	p.His143Gln	missense	Exon 1 of 1	ENSP00000441624.1
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-23726C>A		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-125-23726C>A		intron	N/A	ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46236 AN: 151774 Hom.: 8880 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.359

GnomAD2 exomes AF: 0.416 AC: 104317 AN: 250720 AF XY: 0.430

Gnomad AFR exome AF: 0.0973

Gnomad AMR exome AF: 0.453

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: 0.402

GnomAD4 exome AF: 0.361 AC: 527865 AN: 1460958 Hom.: 104814 Cov.: 51 AF XY: 0.371 AC XY: 269303 AN XY: 726802

African (AFR) AF: 0.0975 AC: 3263 AN: 33468

American (AMR) AF: 0.446 AC: 19947 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13785 AN: 26132

East Asian (EAS) AF: 0.749 AC: 29706 AN: 39684

South Asian (SAS) AF: 0.617 AC: 53192 AN: 86248

European-Finnish (FIN) AF: 0.324 AC: 17313 AN: 53392

Middle Eastern (MID) AF: 0.555 AC: 3198 AN: 5766

European-Non Finnish (NFE) AF: 0.328 AC: 364155 AN: 1111212

Other (OTH) AF: 0.386 AC: 23306 AN: 60366

GnomAD4 genome AF: 0.304 AC: 46249 AN: 151892 Hom.: 8883 Cov.: 32 AF XY: 0.315 AC XY: 23340 AN XY: 74200

African (AFR) AF: 0.106 AC: 4404 AN: 41476

American (AMR) AF: 0.394 AC: 5999 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1829 AN: 3466

East Asian (EAS) AF: 0.736 AC: 3788 AN: 5148

South Asian (SAS) AF: 0.621 AC: 2987 AN: 4808

European-Finnish (FIN) AF: 0.328 AC: 3459 AN: 10532

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22652 AN: 67912

Other (OTH) AF: 0.363 AC: 765 AN: 2110

Alfa AF: 0.344 Hom.: 44184

Bravo AF: 0.301

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.318 AC: 1227

ESP6500AA AF: 0.100 AC: 441

ESP6500EA AF: 0.350 AC: 3013

ExAC AF: 0.411 AC: 49919

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	0.18
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.016
DANN	Benign	0.52
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0051	N
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.94	L
PhyloP100		-1.3
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.0080
Sift	Benign	0.26	T
Sift4G	Benign	0.30	T
Polyphen		0.011	B
Vest4		0.0080
MutPred		0.37		Gain of catalytic residue at H143 (P = 0)
MPC		0.024
ClinPred		0.012	T
GERP RS		-4.8
Varity_R		0.098
gMVP		0.032
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12226920; hg19: chr12-11150046; COSMIC: COSV67856045;