rs2599404

Positions:

• chr12-11133489-A-C

Variant summary

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

The NM_001097643.2(TAS2R30):​c.756T>G​(p.Phe252Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,611,678 control chromosomes in the GnomAD database, including 198,980 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 0.45 (15603 hom., cov: 32)
  • Exomes 𝑓: 0.49 (183377 hom.)
• Consequence: TAS2R30 NM_001097643.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718

Genes affected

TAS2R30 (HGNC:19112): (taste 2 receptor member 30) Enables bitter taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of bitter taste. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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]

PRH1-TAS2R14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.312748E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R30	NM_001097643.2	c.756T>G	p.Phe252Leu	missense_variant	1/1	ENST00000539585.1	NP_001091112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R30	ENST00000539585.1	c.756T>G	p.Phe252Leu	missense_variant	1/1	6	NM_001097643.2	ENSP00000444736.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 67444 AN: 150368 Hom.: 15605 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.421

GnomAD3 exomes AF: 0.444 AC: 111285 AN: 250648 Hom.: 26398 AF XY: 0.438 AC XY: 59467 AN XY: 135792

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.493 AC: 720671 AN: 1461196 Hom.: 183377 Cov.: 97 AF XY: 0.487 AC XY: 353707 AN XY: 726870

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.448 AC: 67456 AN: 150482 Hom.: 15603 Cov.: 32 AF XY: 0.447 AC XY: 32886 AN XY: 73540

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.417

Alfa AF: 0.484 Hom.: 10129

Bravo AF: 0.438

TwinsUK AF: 0.534 AC: 1980

ALSPAC AF: 0.536 AC: 2064

ESP6500AA AF: 0.377 AC: 1662

ESP6500EA AF: 0.504 AC: 4332

ExAC AF: 0.439 AC: 53243

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.084
DANN	Benign	0.21
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.000033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.76	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.019
Sift	Benign	0.67	T
Sift4G	Benign	0.65	T
Vest4		0.044
MutPred		0.41		Loss of methylation at K257 (P = 0.0941);
MPC		0.0047
ClinPred		0.0084	T
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.027
gMVP		0.030

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: rs2599404; hg19: chr12-11286088; COSMIC: COSV67856082;