NM_176888.2:c.418C>T

Variant names:

• chr12-11022154-G-A
• rs1868769
• NM_176888.2:c.418C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_176888.2(TAS2R19):​c.418C>T​(p.Leu140Leu) 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
• Publications: 25 publications found

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]

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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176888.2. 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
	TAS2R19	NM_176888.2	MANE Select	c.418C>T	p.Leu140Leu	synonymous	Exon 1 of 1	NP_795369.1	P59542
	PRH1	NM_001291315.2		c.36+24866C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-126+24866C>T		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R19	ENST00000390673.2	TSL:6 MANE Select	c.418C>T	p.Leu140Leu	synonymous	Exon 1 of 1	ENSP00000375091.2	P59542
	ENSG00000275778	ENST00000536668.2	TSL:5	n.109+12628C>T		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-126+24866C>T		intron	N/A	ENSP00000515364.1	A0A087WYT0

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

GnomAD2 exomes AF: 0.788 AC: 198111 AN: 251252 AF XY: 0.790

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 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

African (AFR) AF: 0.441 AC: 14749 AN: 33466

American (AMR) AF: 0.846 AC: 37813 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 19658 AN: 26124

East Asian (EAS) AF: 0.897 AC: 35594 AN: 39694

South Asian (SAS) AF: 0.742 AC: 63949 AN: 86228

European-Finnish (FIN) AF: 0.850 AC: 45383 AN: 53420

Middle Eastern (MID) AF: 0.766 AC: 4418 AN: 5764

European-Non Finnish (NFE) AF: 0.798 AC: 887603 AN: 1111658

Other (OTH) AF: 0.773 AC: 46659 AN: 60374

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

African (AFR) AF: 0.449 AC: 18554 AN: 41310

American (AMR) AF: 0.794 AC: 12068 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2606 AN: 3418

East Asian (EAS) AF: 0.885 AC: 4565 AN: 5160

South Asian (SAS) AF: 0.761 AC: 3581 AN: 4704

European-Finnish (FIN) AF: 0.857 AC: 9003 AN: 10508

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.803 AC: 54371 AN: 67692

Other (OTH) AF: 0.728 AC: 1533 AN: 2106

Alfa AF: 0.747 Hom.: 20532

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		0.14
PromoterAI		0.0081	Neutral
Mutation Taster		=100/0	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: rs1868769; hg19: chr12-11174753; COSMIC: COSV108225688;