rs10845293

chr12-11030656-G-Achr12-11030656-G-C

Variant summary

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

The NM_176885.2(TAS2R31):c.680C>T(p.Ala227Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,606,516 control chromosomes in the GnomAD database, including 198,239 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (16241 hom., cov: 33)
  • Exomes 𝑓: 0.49 (181998 hom.)
• Consequence: TAS2R31 NM_176885.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

Genes affected

TAS2R31 (HGNC:19113): (taste 2 receptor member 31) TAS2R44 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-TAS2R14 (HGNC:):

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]

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.348526E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R31	NM_176885.2	c.680C>T	p.Ala227Val	missense_variant	1/1	ENST00000390675.2
PRH1-TAS2R14	NM_001316893.2	c.140+4126C>T		intron_variant
PRH1-PRR4	NR_037918.2	n.477+4126C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R31	ENST00000390675.2	c.680C>T	p.Ala227Val	missense_variant	1/1		NM_176885.2	P1
	ENST00000703543.1	c.-126+16364C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 68673 AN: 145448 Hom.: 16241 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.443 AC: 111198 AN: 251076 Hom.: 26312 AF XY: 0.437 AC XY: 59337 AN XY: 135780

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.450

GnomAD4 exome AF: 0.492 AC: 718074 AN: 1460940 Hom.: 181998 Cov.: 127 AF XY: 0.485 AC XY: 352450 AN XY: 726738

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.472 AC: 68688 AN: 145576 Hom.: 16241 Cov.: 33 AF XY: 0.473 AC XY: 33526 AN XY: 70840

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.446

Alfa AF: 0.487 Hom.: 5700

ESP6500AA AF: 0.375 AC: 1652

ESP6500EA AF: 0.500 AC: 4299

ExAC AF: 0.440 AC: 53420

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	13
Dann	Benign	0.96
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.000033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.094
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.63	P
Vest4		0.075
MPC		0.032
ClinPred		0.071	T
GERP RS		1.4
Varity_R		0.079
gMVP		0.051

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: rs10845293; hg19: chr12-11183255; COSMIC: COSV66830382;