Variant rs35720106 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.610

Variant links:

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]

TAS2R43 links:

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]

PRH1 links:

PRH1-TAS2R14 (HGNC:):

PRH1-TAS2R14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2 linkuse as main transcript	c.663C>G	p.Thr221Thr	synonymous_variant	1/1	ENST00000531678.1	NP_795365.2	P59537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R43	ENST00000531678.1 linkuse as main transcript	c.663C>G	p.Thr221Thr	synonymous_variant	1/1	6	NM_176884.2	ENSP00000431719.1		P59537

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

37368

AN:

130286

Hom.:

795

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.404

AC XY:

252614

AN XY:

624956

show subpopulations

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.:

AF XY:

0.295

AC XY:

18671

AN XY:

63212

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely 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

-0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over