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:):

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;