rs1376251

Positions:

• chr12-10986253-C-T

Variant summary

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

The NM_176890.2(TAS2R50):​c.608G>A​(p.Cys203Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,613,636 control chromosomes in the GnomAD database, including 104,649 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.29 (8303 hom., cov: 32)
  • Exomes 𝑓: 0.35 (96346 hom.)
• Consequence: TAS2R50 NM_176890.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

TAS2R50 (HGNC:18882): (taste 2 receptor member 50) TAS2R50 belongs to the large TAS2R receptor family. TAS2Rs are expressed on the surface of taste receptor cells and mediate the perception of bitterness through a G protein-coupled second messenger pathway (Conte et al., 2002 [PubMed 12584440]). See also TAS2R10 (MIM 604791).[supplied by OMIM, Mar 2008]

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=2.0959947E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R50	NM_176890.2	c.608G>A	p.Cys203Tyr	missense_variant	1/1	ENST00000506868.1	NP_795371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R50	ENST00000506868.1	c.608G>A	p.Cys203Tyr	missense_variant	1/1	6	NM_176890.2	ENSP00000424040.1
ENSG00000275778	ENST00000703543.1	c.-125-12532G>A		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44331 AN: 151850 Hom.: 8301 Cov.: 32

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.340

GnomAD3 exomes AF: 0.402 AC: 100937 AN: 251162 Hom.: 23409 AF XY: 0.414 AC XY: 56191 AN XY: 135722

Gnomad AFR exome AF: 0.0914

Gnomad AMR exome AF: 0.442

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.597

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.346 AC: 505178 AN: 1461668 Hom.: 96346 Cov.: 64 AF XY: 0.354 AC XY: 257453 AN XY: 727114

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.292 AC: 44340 AN: 151968 Hom.: 8303 Cov.: 32 AF XY: 0.302 AC XY: 22405 AN XY: 74274

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.344

Alfa AF: 0.325 Hom.: 9321

Bravo AF: 0.287

TwinsUK AF: 0.303 AC: 1122

ALSPAC AF: 0.306 AC: 1178

ESP6500AA AF: 0.0953 AC: 420

ESP6500EA AF: 0.335 AC: 2878

ExAC AF: 0.397 AC: 48164

Asia WGS AF: 0.593 AC: 2056 AN: 3478

EpiCase AF: 0.346

EpiControl AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.90
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.10	N
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Benign	0.41	T
Sift4G	Benign	0.48	T
Polyphen		0.037	B
Vest4		0.19
MPC		0.019
ClinPred		0.028	T
GERP RS		1.2
Varity_R		0.19
gMVP		0.15

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: rs1376251; hg19: chr12-11138852; COSMIC: COSV67855433;