12-11092003-T-C

Position:

• chr12-11092003-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_176884.2(TAS2R43):​c.227A>G​(p.Asn76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0081 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004627675).
• BP6: Variant 12-11092003-T-C is Benign according to our data. Variant chr12-11092003-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 771455.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.227A>G	p.Asn76Ser	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.227A>G	p.Asn76Ser	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4958 AN: 81988 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.00972

Gnomad AMI AF: 0.0646

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0685

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00809 AC: 7261 AN: 897260 Hom.: 0 Cov.: 56 AF XY: 0.00837 AC XY: 3764 AN XY: 449510

Gnomad4 AFR exome AF: 0.000775

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.00615

Gnomad4 EAS exome AF: 0.0238

Gnomad4 SAS exome AF: 0.0162

Gnomad4 FIN exome AF: 0.00805

Gnomad4 NFE exome AF: 0.00683

Gnomad4 OTH exome AF: 0.00750

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0604 AC: 4955 AN: 82080 Hom.: 0 Cov.: 20 AF XY: 0.0656 AC XY: 2584 AN XY: 39382

Gnomad4 AFR AF: 0.00969

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0672 Hom.: 0

ExAC AF: 0.00628 AC: 745

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.67
DANN	Benign	0.45
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.0090
Sift	Benign	0.33	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.23
MPC		0.083
ClinPred		0.098	T
GERP RS		0.73
Varity_R		0.055
gMVP		0.046

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: rs11535673; hg19: chr12-11244602; COSMIC: COSV67860443;