chr12-11091839-C-T

Position:

• chr12-11091839-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_176884.2(TAS2R43):​c.391G>A​(p.Val131Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,476,614 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (9 hom., cov: 23)
  • Exomes 𝑓: 0.0049 (69 hom.)
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26

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 (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-TAS2R14 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01653698).
• BP6: Variant 12-11091839-C-T is Benign according to our data. Variant chr12-11091839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0049 (6602/1346572) while in subpopulation MID AF= 0.039 (221/5664). AF 95% confidence interval is 0.0348. There are 69 homozygotes in gnomad4_exome. There are 3318 alleles in male gnomad4_exome subpopulation. Median coverage is 61. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.391G>A	p.Val131Met	missense_variant	1/1	ENST00000531678.1	NP_795365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R43	ENST00000531678.1	c.391G>A	p.Val131Met	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 654 AN: 129932 Hom.: 9 Cov.: 23

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.000123

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.00673

GnomAD3 exomes AF: 0.00573 AC: 1275 AN: 222438 Hom.: 128 AF XY: 0.00576 AC XY: 701 AN XY: 121782

Gnomad AFR exome AF: 0.000832

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.00366

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.00678

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00490 AC: 6602 AN: 1346572 Hom.: 69 Cov.: 61 AF XY: 0.00492 AC XY: 3318 AN XY: 674750

Gnomad4 AFR exome AF: 0.00133

Gnomad4 AMR exome AF: 0.00525

Gnomad4 ASJ exome AF: 0.0234

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00356

Gnomad4 FIN exome AF: 0.000309

Gnomad4 NFE exome AF: 0.00471

Gnomad4 OTH exome AF: 0.00796

GnomAD4 genome AF: 0.00502 AC: 653 AN: 130042 Hom.: 9 Cov.: 23 AF XY: 0.00497 AC XY: 314 AN XY: 63224

Gnomad4 AFR AF: 0.000994

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00313

Gnomad4 FIN AF: 0.000123

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.00721

Alfa AF: 0.00607 Hom.: 9

ESP6500AA AF: 0.000519 AC: 2

ESP6500EA AF: 0.00710 AC: 58

ExAC AF: 0.00453 AC: 546

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

Oct 01, 2024

TAS2R43: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.31
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.023
Sift	Benign	0.23	T
Sift4G	Benign	0.19	T
Polyphen		0.80	P
Vest4		0.088
MVP		0.22
MPC		0.19
ClinPred		0.018	T
GERP RS		-0.055
Varity_R		0.068
gMVP		0.12

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: rs186718859; hg19: chr12-11244438;