chr12-11092124-A-C

Position:

• chr12-11092124-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176884.2(TAS2R43):​c.106T>G​(p.Phe36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 844,850 control chromosomes in the GnomAD database, including 119,806 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (4565 hom., cov: 22)
  • Exomes 𝑓: 0.51 (115241 hom.)
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035209358).
• BP6: Variant 12-11092124-A-C is Benign according to our data. Variant chr12-11092124-A-C is described in ClinVar as [Benign]. Clinvar id is 768523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.106T>G	p.Phe36Val	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.106T>G	p.Phe36Val	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 37489 AN: 89942 Hom.: 4564 Cov.: 22

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.435

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.00158 AC: 309 AN: 195486 Hom.: 117 AF XY: 0.00133 AC XY: 143 AN XY: 107148

Gnomad AFR exome AF: 0.000450

Gnomad AMR exome AF: 0.000288

Gnomad ASJ exome AF: 0.000781

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000353

Gnomad FIN exome AF: 0.00959

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00208

GnomAD4 exome AF: 0.511 AC: 385643 AN: 754796 Hom.: 115241 Cov.: 59 AF XY: 0.511 AC XY: 192624 AN XY: 376644

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.416 AC: 37496 AN: 90054 Hom.: 4565 Cov.: 22 AF XY: 0.419 AC XY: 18345 AN XY: 43804

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.415

Alfa AF: 0.526 Hom.: 1913

ExAC AF: 0.0428 AC: 4469

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.016
DANN	Benign	0.24
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	4.0	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.14
ClinPred		0.0065	T
GERP RS		-0.47
Varity_R		0.031
gMVP		0.057

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs191086711; hg19: chr12-11244723; COSMIC: COSV67852533;