rs10845293

Positions:

• chr12-11030656-G-A
• chr12-11030656-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]

ENSG00000275778 (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]

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	Protein	UniProt
TAS2R31	NM_176885.2	c.680C>T	p.Ala227Val	missense_variant	1/1	ENST00000390675.2	NP_795366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R31	ENST00000390675.2	c.680C>T	p.Ala227Val	missense_variant	1/1	6	NM_176885.2	ENSP00000375093.2
ENSG00000275778	ENST00000703543.1	c.-126+16364C>T		intron_variant				ENSP00000515364.1

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
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;