chr12-11021677-G-A

Position:

• 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]

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]

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	Protein	UniProt
TAS2R19	NM_176888.2	c.895C>T	p.Arg299Cys	missense_variant	1/1	ENST00000390673.2	NP_795369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R19	ENST00000390673.2	c.895C>T	p.Arg299Cys	missense_variant	1/1	6	NM_176888.2	ENSP00000375091.2
ENSG00000275778	ENST00000703543.1	c.-126+25343C>T		intron_variant				ENSP00000515364.1

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;