12-11091518-A-G

Position:

• chr12-11091518-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176884.2(TAS2R43):​c.712T>C​(p.Cys238Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,280,436 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (1034 hom., cov: 24)
  • Exomes 𝑓: 0.072 (16812 hom.)
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032700896).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.712T>C	p.Cys238Arg	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.712T>C	p.Cys238Arg	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 10832 AN: 114512 Hom.: 1033 Cov.: 24

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0659

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0798

GnomAD3 exomes AF: 0.0212 AC: 4553 AN: 214462 Hom.: 449 AF XY: 0.0212 AC XY: 2479 AN XY: 116798

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.00480

Gnomad EAS exome AF: 0.00770

Gnomad SAS exome AF: 0.00361

Gnomad FIN exome AF: 0.0251

Gnomad NFE exome AF: 0.0321

Gnomad OTH exome AF: 0.0155

GnomAD4 exome AF: 0.0716 AC: 83521 AN: 1165822 Hom.: 16812 Cov.: 53 AF XY: 0.0730 AC XY: 42526 AN XY: 582680

Gnomad4 AFR exome AF: 0.0472

Gnomad4 AMR exome AF: 0.0835

Gnomad4 ASJ exome AF: 0.0366

Gnomad4 EAS exome AF: 0.0503

Gnomad4 SAS exome AF: 0.0353

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0730

Gnomad4 OTH exome AF: 0.0708

GnomAD4 genome AF: 0.0945 AC: 10836 AN: 114614 Hom.: 1034 Cov.: 24 AF XY: 0.0955 AC XY: 5325 AN XY: 55762

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.0652

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.0993 Hom.: 481

ExAC AF: 0.0706 AC: 8520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.58
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.077	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.078
Sift	Benign	0.075	T
Sift4G	Benign	0.098	T
Polyphen		0.0010	B
Vest4		0.13
MPC		0.19
ClinPred		0.0063	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.33
gMVP		0.16

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: rs3759245; hg19: chr12-11244117; COSMIC: COSV67851513;