12-11092145-G-A

Position:

• chr12-11092145-G-A

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.85C>T​(p.Leu29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 716,618 control chromosomes in the GnomAD database, including 70,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (1868 hom., cov: 21)
  • Exomes 𝑓: 0.35 (68293 hom.)
• Consequence: TAS2R43 NM_176884.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.373

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=-0.86).
• BP6: Variant 12-11092145-G-A is Benign according to our data. Variant chr12-11092145-G-A is described in ClinVar as [Benign]. Clinvar id is 768526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.373 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.85C>T	p.Leu29=	synonymous_variant	1/1	ENST00000531678.1	NP_795365.2
PRH1-TAS2R14	NM_001316893.2	c.-133-44957C>T		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.205-44957C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R43	ENST00000531678.1	c.85C>T	p.Leu29=	synonymous_variant	1/1		NM_176884.2	ENSP00000431719	P1
TAS2R14	ENST00000381852.4	n.153-44957C>T		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5	n.124-44957C>T		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1	n.358+28865C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.336 AC: 25391 AN: 75618 Hom.: 1868 Cov.: 21

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.337

GnomAD3 exomes AF: 0.00126 AC: 248 AN: 196082 Hom.: 93 AF XY: 0.00118 AC XY: 127 AN XY: 107620

Gnomad AFR exome AF: 0.000525

Gnomad AMR exome AF: 0.000468

Gnomad ASJ exome AF: 0.000447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000353

Gnomad FIN exome AF: 0.00594

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.000834

GnomAD4 exome AF: 0.354 AC: 226627 AN: 640870 Hom.: 68293 Cov.: 43 AF XY: 0.361 AC XY: 115716 AN XY: 320734

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.335 AC: 25398 AN: 75748 Hom.: 1868 Cov.: 21 AF XY: 0.340 AC XY: 12490 AN XY: 36702

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.335

Alfa AF: 0.490 Hom.: 1862

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
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: rs201819808; hg19: chr12-11244744; COSMIC: COSV67856726;