chr12-11030656-G-A

Variant names:

• chr12-11030656-G-A
• rs10845293
• NM_176885.2:c.680C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 40 publications found

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]

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176885.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R31	NM_176885.2	MANE Select	c.680C>T	p.Ala227Val	missense	Exon 1 of 1	NP_795366.2
	PRH1	NM_001291315.2		c.36+16364C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-126+16364C>T		intron	N/A	NP_001278243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R31	ENST00000390675.2	TSL:6 MANE Select	c.680C>T	p.Ala227Val	missense	Exon 1 of 1	ENSP00000375093.2
	ENSG00000275778	ENST00000536668.2	TSL:5	n.109+4126C>T		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-126+16364C>T		intron	N/A	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

GnomAD2 exomes AF: 0.443 AC: 111198 AN: 251076 AF XY: 0.437

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 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

African (AFR) AF: 0.366 AC: 12241 AN: 33470

American (AMR) AF: 0.445 AC: 19869 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9006 AN: 26098

East Asian (EAS) AF: 0.225 AC: 8918 AN: 39660

South Asian (SAS) AF: 0.278 AC: 23890 AN: 86058

European-Finnish (FIN) AF: 0.600 AC: 32030 AN: 53396

Middle Eastern (MID) AF: 0.322 AC: 1852 AN: 5754

European-Non Finnish (NFE) AF: 0.524 AC: 582701 AN: 1111486

Other (OTH) AF: 0.457 AC: 27567 AN: 60330

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

African (AFR) AF: 0.368 AC: 15041 AN: 40884

American (AMR) AF: 0.473 AC: 6777 AN: 14336

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1172 AN: 3194

East Asian (EAS) AF: 0.275 AC: 1168 AN: 4246

South Asian (SAS) AF: 0.320 AC: 1309 AN: 4096

European-Finnish (FIN) AF: 0.622 AC: 6299 AN: 10126

Middle Eastern (MID) AF: 0.377 AC: 95 AN: 252

European-Non Finnish (NFE) AF: 0.539 AC: 35346 AN: 65562

Other (OTH) AF: 0.446 AC: 891 AN: 1996

Alfa AF: 0.485 Hom.: 5743

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 v4.9

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
PhyloP100		0.49
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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