12-10997170-T-C

Position:

• chr12-10997170-T-C

Variant summary

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

The NM_176889.4(TAS2R20):​c.706A>G​(p.Ile236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,804 control chromosomes in the GnomAD database, including 113,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.30 (8925 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104826 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

TAS2R20 (HGNC:19109): (taste 2 receptor member 20) This gene encodes a member of the taste receptor two family of class C G-protein coupled receptors. Receptors of this family have a short extracellular N-terminus, seven transmembrane helices, three extracellular loops and three intracellular loops, and an intracellular C-terminus. Members of this family are expressed in a subset of taste receptor cells, where they function in bitter taste reception, as well as in non-gustatory cells including those of the brain, reproductive organs, respiratory system, and gastrointestinal system. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2016]

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=1.1594881E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.706A>G	p.Ile236Val	missense_variant	1/1	ENST00000538986.2	NP_795370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2	c.706A>G	p.Ile236Val	missense_variant	1/1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000703543.1	c.-125-23449A>G		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46333 AN: 151992 Hom.: 8922 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.416 AC: 104511 AN: 251092 Hom.: 24986 AF XY: 0.430 AC XY: 58396 AN XY: 135690

Gnomad AFR exome AF: 0.0976

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.361 AC: 528251 AN: 1461694 Hom.: 104826 Cov.: 50 AF XY: 0.371 AC XY: 269483 AN XY: 727136

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.305 AC: 46346 AN: 152110 Hom.: 8925 Cov.: 32 AF XY: 0.315 AC XY: 23394 AN XY: 74338

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.363

Alfa AF: 0.347 Hom.: 14363

Bravo AF: 0.301

TwinsUK AF: 0.321 AC: 1191

ALSPAC AF: 0.321 AC: 1238

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.351 AC: 3016

ExAC AF: 0.411 AC: 49945

Asia WGS AF: 0.609 AC: 2112 AN: 3478

EpiCase AF: 0.366

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.34
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0073	N
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.042
Sift	Benign	0.057	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.015
MPC		0.022
ClinPred		0.0041	T
GERP RS		-1.6
Varity_R		0.061
gMVP		0.017

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10845281; hg19: chr12-11149769; COSMIC: COSV67856042;