12-11022154-G-A

Position:

• chr12-11022154-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_176888.2(TAS2R19):​c.418C>T​(p.Leu140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,612,746 control chromosomes in the GnomAD database, including 499,872 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 0.71 (39761 hom., cov: 33)
  • Exomes 𝑓: 0.79 (460111 hom.)
• Consequence: TAS2R19 NM_176888.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

TAS2R19 (HGNC:19108): (taste 2 receptor member 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of taste. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP7: Synonymous conserved (PhyloP=0.137 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R19	NM_176888.2	c.418C>T	p.Leu140=	synonymous_variant	1/1	ENST00000390673.2	NP_795369.1
PRH1-TAS2R14	NM_001316893.2	c.140+12628C>T		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.477+12628C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R19	ENST00000390673.2	c.418C>T	p.Leu140=	synonymous_variant	1/1		NM_176888.2	ENSP00000375091	P1
	ENST00000703543.1	c.-126+24866C>T		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107208 AN: 151182 Hom.: 39747 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.726

GnomAD3 exomes AF: 0.788 AC: 198111 AN: 251252 Hom.: 79398 AF XY: 0.790 AC XY: 107294 AN XY: 135802

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.880

Gnomad SAS exome AF: 0.752

Gnomad FIN exome AF: 0.849

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.791 AC: 1155826 AN: 1461438 Hom.: 460111 Cov.: 55 AF XY: 0.790 AC XY: 574493 AN XY: 727008

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.752

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.773

GnomAD4 genome AF: 0.709 AC: 107243 AN: 151308 Hom.: 39761 Cov.: 33 AF XY: 0.714 AC XY: 52841 AN XY: 73980

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.728

Alfa AF: 0.751 Hom.: 20457

Bravo AF: 0.692

Asia WGS AF: 0.800 AC: 2779 AN: 3476

EpiCase AF: 0.795

EpiControl AF: 0.792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1868769; hg19: chr12-11174753;