12-11062271-A-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_176887.2(TAS2R46):c.24T>A(p.Ile8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R46 NM_176887.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

Genes affected

TAS2R46 (HGNC:18877): (taste 2 receptor member 46) TAS2R46 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, Sep 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 12-11062271-A-T is Benign according to our data. Variant chr12-11062271-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R46	NM_176887.2	c.24T>A	p.Ile8=	synonymous_variant	1/1	ENST00000533467.1
PRH1-TAS2R14	NM_001316893.2	c.-133-15083T>A		intron_variant
PRH1-PRR4	NR_037918.2	n.205-15083T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R46	ENST00000533467.1	c.24T>A	p.Ile8=	synonymous_variant	1/1		NM_176887.2	P1
TAS2R14	ENST00000381852.4	n.153-15083T>A		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5	n.124-15083T>A		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1	n.359-15083T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 22 AN: 145054 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.000675

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000155

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000215 AC: 294 AN: 1367486 Hom.: 0 Cov.: 37 AF XY: 0.000258 AC XY: 175 AN XY: 679000

Gnomad4 AFR exome AF: 0.0000920

Gnomad4 AMR exome AF: 0.000618

Gnomad4 ASJ exome AF: 0.000330

Gnomad4 EAS exome AF: 0.000270

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.000236

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000354

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000152 AC: 22 AN: 145180 Hom.: 0 Cov.: 32 AF XY: 0.000253 AC XY: 18 AN XY: 71008

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000304

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.000675

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000155

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00136 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

TAS2R46: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.4
Dann	Benign	0.59

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: rs200226376; hg19: chr12-11214870; COSMIC: COSV67862224;