rs10772420

chr12-11021677-G-A

Variant summary

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

The NM_176888.2(TAS2R19):c.895C>T(p.Arg299Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,358,012 control chromosomes in the GnomAD database, including 181,501 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (16550 hom., cov: 48)
  • Exomes 𝑓: 0.53 (181501 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R19 NM_176888.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.8176775E-4).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R19	NM_176888.2	c.895C>T	p.Arg299Cys	missense_variant	1/1	ENST00000390673.2
PRH1-TAS2R14	NM_001316893.2	c.140+13105C>T		intron_variant
PRH1-PRR4	NR_037918.2	n.477+13105C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R19	ENST00000390673.2	c.895C>T	p.Arg299Cys	missense_variant	1/1		NM_176888.2	P1
	ENST00000703543.1	c.-126+25343C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 83208 AN: 148308 Hom.: 16551 Cov.: 48 FAILED QC

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.530

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.558

GnomAD3 exomes AF: 0.450 AC: 110094 AN: 244806 Hom.: 26022 AF XY: 0.444 AC XY: 58765 AN XY: 132380

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.221

Gnomad SAS exome AF: 0.282

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.533 AC: 723948 AN: 1358012 Hom.: 181501 Cov.: 40 AF XY: 0.532 AC XY: 355172 AN XY: 668102

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.561 AC: 83219 AN: 148418 Hom.: 16550 Cov.: 48 AF XY: 0.563 AC XY: 40839 AN XY: 72486

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.557

Alfa AF: 0.487 Hom.: 36551

TwinsUK AF: 0.532 AC: 1973

ALSPAC AF: 0.533 AC: 2053

ESP6500AA AF: 0.379 AC: 1670

ESP6500EA AF: 0.501 AC: 4311

ExAC AF: 0.455 AC: 55212

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00020	N
MetaRNN	Benign	0.00038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.9	N
REVEL	Benign	0.029
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.036
MPC		0.016
ClinPred		0.021	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.034

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: rs10772420; hg19: chr12-11174276; COSMIC: COSV66827944;