12-11092131-A-G

Position:

• chr12-11092131-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_176884.2(TAS2R43):​c.99T>C​(p.Ile33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 794,654 control chromosomes in the GnomAD database, including 101,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (3220 hom., cov: 22)
  • Exomes 𝑓: 0.46 (98184 hom.)
• Consequence: TAS2R43 NM_176884.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.923

Genes affected

TAS2R43 (HGNC:18875): (taste 2 receptor member 43) TAS2R43 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]). For further information on TAS2Rs, see MIM 604791.[supplied by OMIM, Mar 2009]

PRH1-TAS2R14 (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]

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-11092131-A-G is Benign according to our data. Variant chr12-11092131-A-G is described in ClinVar as [Benign]. Clinvar id is 768524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.923 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R43	NM_176884.2	c.99T>C	p.Ile33=	synonymous_variant	1/1	ENST00000531678.1
PRH1-TAS2R14	NM_001316893.2	c.-133-44943T>C		intron_variant
PRH1-PRR4	NR_037918.2	n.205-44943T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R43	ENST00000531678.1	c.99T>C	p.Ile33=	synonymous_variant	1/1		NM_176884.2	P1
TAS2R14	ENST00000381852.4	n.153-44943T>C		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5	n.124-44943T>C		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1	n.358+28879T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 31829 AN: 83030 Hom.: 3219 Cov.: 22

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.387

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.384

GnomAD3 exomes AF: 0.00106 AC: 208 AN: 196882 Hom.: 75 AF XY: 0.000880 AC XY: 95 AN XY: 107894

Gnomad AFR exome AF: 0.000373

Gnomad AMR exome AF: 0.000287

Gnomad ASJ exome AF: 0.000556

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00515

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.459 AC: 326675 AN: 711506 Hom.: 98184 Cov.: 48 AF XY: 0.462 AC XY: 163941 AN XY: 354798

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.383 AC: 31838 AN: 83148 Hom.: 3220 Cov.: 22 AF XY: 0.387 AC XY: 15638 AN XY: 40454

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.382

Alfa AF: 0.513 Hom.: 1897

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 25, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199862459; hg19: chr12-11244730;