12-11091567-G-C

Variant names:

• chr12-11091567-G-C
• rs35720106
• NM_176884.2:c.663C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_176884.2(TAS2R43):​c.663C>G​(p.Thr221Thr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.610
• Publications: 16 publications found

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]

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 -21 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 VariationId is 769815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.663C>G	p.Thr221Thr	synonymous_variant	Exon 1 of 1	ENST00000531678.1	NP_795365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R43	ENST00000531678.1	c.663C>G	p.Thr221Thr	synonymous_variant	Exon 1 of 1	6	NM_176884.2	ENSP00000431719.1
ENSG00000275778	ENST00000536668.2	n.-164-44379C>G		intron_variant	Intron 1 of 9	5		ENSP00000482961.1

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

GnomAD2 exomes AF: 0.473 AC: 102257 AN: 216294 AF XY: 0.481

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 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

African (AFR) AF: 0.105 AC: 3291 AN: 31368

American (AMR) AF: 0.426 AC: 17452 AN: 40968

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 12085 AN: 24238

East Asian (EAS) AF: 0.618 AC: 23247 AN: 37588

South Asian (SAS) AF: 0.574 AC: 46043 AN: 80222

European-Finnish (FIN) AF: 0.338 AC: 16249 AN: 48142

Middle Eastern (MID) AF: 0.480 AC: 2609 AN: 5438

European-Non Finnish (NFE) AF: 0.386 AC: 356191 AN: 922690

Other (OTH) AF: 0.405 AC: 21579 AN: 53236

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

African (AFR) AF: 0.111 AC: 4123 AN: 37072

American (AMR) AF: 0.374 AC: 4782 AN: 12776

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1362 AN: 3256

East Asian (EAS) AF: 0.497 AC: 2383 AN: 4798

South Asian (SAS) AF: 0.463 AC: 2041 AN: 4406

European-Finnish (FIN) AF: 0.361 AC: 2862 AN: 7932

Middle Eastern (MID) AF: 0.401 AC: 109 AN: 272

European-Non Finnish (NFE) AF: 0.330 AC: 18923 AN: 57326

Other (OTH) AF: 0.335 AC: 607 AN: 1814

Alfa AF: 0.330 Hom.: 1237

Asia WGS AF: 0.852 AC: 2693 AN: 3166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 25, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35720106; hg19: chr12-11244166; COSMIC: COSV67851583;