rs35720106

Positions:

• chr12-11091567-G-C
• chr12-11091567-G-T

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.663C>G​(p.Thr221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,374,296 control chromosomes in the GnomAD database, including 94,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (796 hom., cov: 23)
  • Exomes 𝑓: 0.40 (93514 hom.)
• Consequence: TAS2R43 NM_176884.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.610

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=-0.95).
• BP6: Variant 12-11091567-G-C is Benign according to our data. Variant chr12-11091567-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 769815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R43	NM_176884.2	c.663C>G	p.Thr221=	synonymous_variant	1/1	ENST00000531678.1
PRH1-TAS2R14	NM_001316893.2	c.-133-44379C>G		intron_variant
PRH1-PRR4	NR_037918.2	n.205-44379C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R43	ENST00000531678.1	c.663C>G	p.Thr221=	synonymous_variant	1/1		NM_176884.2	P1
TAS2R14	ENST00000381852.4	n.153-44379C>G		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000541977.5	n.124-44379C>G		intron_variant, non_coding_transcript_variant		2
PRH1	ENST00000546265.1	n.358+29443C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 37368 AN: 130286 Hom.: 795 Cov.: 23

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.473 AC: 102257 AN: 216294 Hom.: 25401 AF XY: 0.481 AC XY: 56593 AN XY: 117662

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.568

Gnomad EAS exome AF: 0.726

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.401 AC: 498746 AN: 1243890 Hom.: 93514 Cov.: 59 AF XY: 0.404 AC XY: 252614 AN XY: 624956

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.499

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.287 AC: 37378 AN: 130406 Hom.: 796 Cov.: 23 AF XY: 0.295 AC XY: 18671 AN XY: 63212

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.335

Alfa AF: 0.330 Hom.: 1237

Asia WGS AF: 0.852 AC: 2693 AN: 3166

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

Invitae

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35720106; hg19: chr12-11244166; COSMIC: COSV67851583;