chr12-10986253-C-T

Variant names:

• chr12-10986253-C-T
• rs1376251
• NM_176890.2:c.608G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 0.29 (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
• Publications: 66 publications found

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]

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=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 rank	MANE	Protein	UniProt
TAS2R50	NM_176890.2	c.608G>A	p.Cys203Tyr	missense_variant	Exon 1 of 1	ENST00000506868.1	NP_795371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R50	ENST00000506868.1	c.608G>A	p.Cys203Tyr	missense_variant	Exon 1 of 1	6	NM_176890.2	ENSP00000424040.1
ENSG00000275778	ENST00000536668.2	n.110-12532G>A		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

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

GnomAD2 exomes AF: 0.402 AC: 100937 AN: 251162 AF XY: 0.414

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 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

African (AFR) AF: 0.0899 AC: 3008 AN: 33474

American (AMR) AF: 0.436 AC: 19475 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12933 AN: 26120

East Asian (EAS) AF: 0.748 AC: 29709 AN: 39698

South Asian (SAS) AF: 0.586 AC: 50526 AN: 86220

European-Finnish (FIN) AF: 0.321 AC: 17135 AN: 53408

Middle Eastern (MID) AF: 0.521 AC: 3006 AN: 5766

European-Non Finnish (NFE) AF: 0.312 AC: 347047 AN: 1111876

Other (OTH) AF: 0.370 AC: 22339 AN: 60392

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

African (AFR) AF: 0.0991 AC: 4106 AN: 41424

American (AMR) AF: 0.376 AC: 5737 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1717 AN: 3464

East Asian (EAS) AF: 0.736 AC: 3802 AN: 5168

South Asian (SAS) AF: 0.589 AC: 2840 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3454 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21625 AN: 67946

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.327 Hom.: 15849

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
PhyloP100		1.6
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
Mutation Taster		=94/6	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: rs1376251; hg19: chr12-11138852; COSMIC: COSV67855433;