NM_176889.4:c.442C>A

Variant names:

• chr12-10997434-G-T
• rs12226919
• NM_176889.4:c.442C>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.442C>A​(p.His148Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,336 control chromosomes in the GnomAD database, including 113,912 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H148P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.31 (8996 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104916 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 47 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=3.1288212E-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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R20	NM_176889.4	MANE Select	c.442C>A	p.His148Asn	missense	Exon 1 of 1	NP_795370.2	P59543
	PRH1	NM_001291315.2		c.37-23713C>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-23713C>A		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.442C>A	p.His148Asn	missense	Exon 1 of 1	ENSP00000441624.1	P59543
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-23713C>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-125-23713C>A		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46963 AN: 151908 Hom.: 8993 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.362

GnomAD2 exomes AF: 0.417 AC: 104703 AN: 250858 AF XY: 0.431

Gnomad AFR exome AF: 0.115

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: 0.348

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.362 AC: 528688 AN: 1461310 Hom.: 104916 Cov.: 49 AF XY: 0.371 AC XY: 269636 AN XY: 726958

African (AFR) AF: 0.114 AC: 3821 AN: 33476

American (AMR) AF: 0.447 AC: 19973 AN: 44688

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

East Asian (EAS) AF: 0.748 AC: 29703 AN: 39688

South Asian (SAS) AF: 0.617 AC: 53193 AN: 86248

European-Finnish (FIN) AF: 0.324 AC: 17313 AN: 53390

Middle Eastern (MID) AF: 0.555 AC: 3202 AN: 5766

European-Non Finnish (NFE) AF: 0.328 AC: 364331 AN: 1111546

Other (OTH) AF: 0.387 AC: 23369 AN: 60380

GnomAD4 genome AF: 0.309 AC: 46974 AN: 152026 Hom.: 8996 Cov.: 32 AF XY: 0.319 AC XY: 23669 AN XY: 74294

African (AFR) AF: 0.122 AC: 5048 AN: 41528

American (AMR) AF: 0.395 AC: 6021 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3798 AN: 5160

South Asian (SAS) AF: 0.621 AC: 2985 AN: 4806

European-Finnish (FIN) AF: 0.330 AC: 3479 AN: 10558

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

European-Non Finnish (NFE) AF: 0.334 AC: 22672 AN: 67938

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.343 Hom.: 41456

Bravo AF: 0.306

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.318 AC: 1227

ESP6500AA AF: 0.119 AC: 524

ESP6500EA AF: 0.350 AC: 3014

ExAC AF: 0.413 AC: 50126

Asia WGS AF: 0.609 AC: 2113 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	0.056
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.046
DANN	Benign	0.34
DEOGEN2	Benign	0.00039	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00014	N
MetaRNN	Benign	0.0000031	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-2.6	N
PhyloP100		-0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	3.0	N
REVEL	Benign	0.081
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.024
ClinPred		0.010	T
GERP RS		0.52
Varity_R		0.038
gMVP		0.024
Mutation Taster		=95/5	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: rs12226919; hg19: chr12-11150033; COSMIC: COSV67856631;