12-11092124-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:):

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;