12-11091839-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:):

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;