12-10996933-A-G

Position:

• chr12-10996933-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176889.4(TAS2R20):​c.*13T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,574,768 control chromosomes in the GnomAD database, including 110,006 homozygotes. In-silico tool predicts 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 (8930 hom., cov: 32)
  • Exomes 𝑓: 0.36 (101076 hom.)
• Consequence: TAS2R20 NM_176889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16

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]

PRH1-TAS2R14 (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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R20	NM_176889.4	c.*13T>C		3_prime_UTR_variant	1/1	ENST00000538986.2
PRH1-TAS2R14	NM_001316893.2	c.141-23212T>C		intron_variant
PRH1-PRR4	NR_037918.2	n.478-23212T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R20	ENST00000538986.2	c.*13T>C		3_prime_UTR_variant	1/1		NM_176889.4	P1
	ENST00000703543.1	c.-125-23212T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46320 AN: 151838 Hom.: 8928 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.411 AC: 94876 AN: 230902 Hom.: 22475 AF XY: 0.425 AC XY: 52960 AN XY: 124686

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.629

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.360 AC: 511509 AN: 1422814 Hom.: 101076 Cov.: 31 AF XY: 0.368 AC XY: 259113 AN XY: 703558

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.305 AC: 46331 AN: 151954 Hom.: 8930 Cov.: 32 AF XY: 0.315 AC XY: 23401 AN XY: 74256

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.363

Alfa AF: 0.347 Hom.: 4106

Bravo AF: 0.301

Asia WGS AF: 0.608 AC: 2109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1450839; hg19: chr12-11149532; COSMIC: COSV67854936;