12-11092122-G-C

Position:

• chr12-11092122-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176884.2(TAS2R43):​c.108C>G​(p.Phe36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 874,090 control chromosomes in the GnomAD database, including 121,120 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 (4887 hom., cov: 22)
  • Exomes 𝑓: 0.51 (116233 hom.)
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131

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=0.002693683).
• BP6: Variant 12-11092122-G-C is Benign according to our data. Variant chr12-11092122-G-C is described in ClinVar as [Benign]. Clinvar id is 768522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.108C>G	p.Phe36Leu	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.108C>G	p.Phe36Leu	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 38770 AN: 91448 Hom.: 4885 Cov.: 22

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.00274 AC: 531 AN: 194040 Hom.: 197 AF XY: 0.00234 AC XY: 249 AN XY: 106340

Gnomad AFR exome AF: 0.000680

Gnomad AMR exome AF: 0.000943

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.000233

Gnomad SAS exome AF: 0.0000709

Gnomad FIN exome AF: 0.0177

Gnomad NFE exome AF: 0.00286

Gnomad OTH exome AF: 0.00355

GnomAD4 exome AF: 0.512 AC: 400849 AN: 782526 Hom.: 116233 Cov.: 59 AF XY: 0.513 AC XY: 199926 AN XY: 389728

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.424 AC: 38782 AN: 91564 Hom.: 4887 Cov.: 22 AF XY: 0.426 AC XY: 18973 AN XY: 44528

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.430

Alfa AF: 0.524 Hom.: 1806

ExAC AF: 0.0429 AC: 4474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	0.24
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.078
Sift	Benign	0.036	D
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.47		Loss of methylation at K37 (P = 0.0386);
MPC		0.12
ClinPred		0.0038	T
GERP RS		2.0
Varity_R		0.072
gMVP		0.044

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: rs201281372; hg19: chr12-11244721; COSMIC: COSV67852532;