rs10772420

Variant names:

• chr12-11021677-G-A
• rs10772420
• NM_176888.2:c.895C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 64 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 -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.

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.895C>T	p.Arg299Cys	missense	Exon 1 of 1	NP_795369.1	P59542
	PRH1	NM_001291315.2		c.36+25343C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-126+25343C>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.895C>T	p.Arg299Cys	missense	Exon 1 of 1	ENSP00000375091.2	P59542
	ENSG00000275778	ENST00000536668.2	TSL:5	n.109+13105C>T		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-126+25343C>T		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.561 AC: 83208 AN: 148308 Hom.: 16551 Cov.: 48

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

GnomAD2 exomes AF: 0.450 AC: 110094 AN: 244806 AF XY: 0.444

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 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

African (AFR) AF: 0.375 AC: 12190 AN: 32530

American (AMR) AF: 0.519 AC: 20056 AN: 38652

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 9369 AN: 22226

East Asian (EAS) AF: 0.430 AC: 10561 AN: 24544

South Asian (SAS) AF: 0.377 AC: 25144 AN: 66612

European-Finnish (FIN) AF: 0.675 AC: 32751 AN: 48536

Middle Eastern (MID) AF: 0.441 AC: 2208 AN: 5006

European-Non Finnish (NFE) AF: 0.548 AC: 583698 AN: 1064800

Other (OTH) AF: 0.508 AC: 27971 AN: 55106

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

African (AFR) AF: 0.417 AC: 16856 AN: 40428

American (AMR) AF: 0.589 AC: 8699 AN: 14764

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1851 AN: 3358

East Asian (EAS) AF: 0.525 AC: 2666 AN: 5078

South Asian (SAS) AF: 0.525 AC: 2432 AN: 4634

European-Finnish (FIN) AF: 0.679 AC: 7086 AN: 10430

Middle Eastern (MID) AF: 0.529 AC: 148 AN: 280

European-Non Finnish (NFE) AF: 0.627 AC: 41702 AN: 66492

Other (OTH) AF: 0.557 AC: 1144 AN: 2054

Alfa AF: 0.480 Hom.: 51313

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 v4.9

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
PhyloP100		-0.044
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
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: rs10772420; hg19: chr12-11174276; COSMIC: COSV66827944;