12-10986084-C-T

Variant names:

• chr12-10986084-C-T
• rs10772397
• NM_176890.2:c.777G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_176890.2(TAS2R50):​c.777G>A​(p.Pro259Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,658 control chromosomes in the GnomAD database, including 291,138 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (22695 hom., cov: 32)
  • Exomes 𝑓: 0.60 (268443 hom.)
• Consequence: TAS2R50 NM_176890.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45
• Publications: 56 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-4.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176890.2. 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
	TAS2R50	NM_176890.2	MANE Select	c.777G>A	p.Pro259Pro	synonymous	Exon 1 of 1	NP_795371.2	P59544
	PRH1	NM_001291315.2		c.37-12363G>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-125-12363G>A		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R50	ENST00000506868.1	TSL:6 MANE Select	c.777G>A	p.Pro259Pro	synonymous	Exon 1 of 1	ENSP00000424040.1	P59544
	ENSG00000275778	ENST00000536668.2	TSL:5	n.110-12363G>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-125-12363G>A		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78660 AN: 151808 Hom.: 22697 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.617 AC: 154963 AN: 251206 AF XY: 0.626

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.668

Gnomad EAS exome AF: 0.753

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.611

Gnomad OTH exome AF: 0.623

GnomAD4 exome AF: 0.602 AC: 880305 AN: 1461732 Hom.: 268443 Cov.: 68 AF XY: 0.606 AC XY: 440703 AN XY: 727146

African (AFR) AF: 0.233 AC: 7800 AN: 33474

American (AMR) AF: 0.641 AC: 28640 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 17564 AN: 26134

East Asian (EAS) AF: 0.750 AC: 29761 AN: 39694

South Asian (SAS) AF: 0.678 AC: 58445 AN: 86230

European-Finnish (FIN) AF: 0.649 AC: 34645 AN: 53416

Middle Eastern (MID) AF: 0.672 AC: 3874 AN: 5768

European-Non Finnish (NFE) AF: 0.597 AC: 663436 AN: 1111910

Other (OTH) AF: 0.598 AC: 36140 AN: 60392

GnomAD4 genome AF: 0.518 AC: 78669 AN: 151926 Hom.: 22695 Cov.: 32 AF XY: 0.526 AC XY: 39041 AN XY: 74272

African (AFR) AF: 0.246 AC: 10158 AN: 41374

American (AMR) AF: 0.604 AC: 9214 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2338 AN: 3466

East Asian (EAS) AF: 0.741 AC: 3827 AN: 5168

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4818

European-Finnish (FIN) AF: 0.649 AC: 6862 AN: 10568

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40990 AN: 67956

Other (OTH) AF: 0.556 AC: 1170 AN: 2106

Alfa AF: 0.578 Hom.: 47991

Bravo AF: 0.503

Asia WGS AF: 0.655 AC: 2274 AN: 3478

EpiCase AF: 0.617

EpiControl AF: 0.612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-4.5
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: rs10772397; hg19: chr12-11138683; COSMIC: COSV104702520;