chr12-11092043-A-C

Position:

• chr12-11092043-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_176884.2(TAS2R43):​c.187T>G​(p.Leu63Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12116805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R43	NM_176884.2	c.187T>G	p.Leu63Val	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.187T>G	p.Leu63Val	missense_variant	1/1	6	NM_176884.2	ENSP00000431719.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000450 AC: 10 AN: 221992 Hom.: 0 AF XY: 0.0000247 AC XY: 3 AN XY: 121240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000336

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000248 AC: 34 AN: 1371824 Hom.: 0 Cov.: 64 AF XY: 0.0000190 AC XY: 13 AN XY: 685568

Gnomad4 AFR exome AF: 0.0000619

Gnomad4 AMR exome AF: 0.000264

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000154

Gnomad4 OTH exome AF: 0.0000523

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000167 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.187T>G (p.L63V) alteration is located in exon 1 (coding exon 1) of the TAS2R43 gene. This alteration results from a T to G substitution at nucleotide position 187, causing the leucine (L) at amino acid position 63 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.14
DANN	Benign	0.87
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.035
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.058	T
Polyphen		0.025	B
Vest4		0.31
MutPred		0.62		Gain of MoRF binding (P = 0.1797);
MVP		0.18
MPC		0.12
ClinPred		0.078	T
GERP RS		-1.9
Varity_R		0.25
gMVP		0.076

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: rs759861245; hg19: chr12-11244642;