12-10997641-T-C

Position:

• chr12-10997641-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.235A>G​(p.Lys79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,478 control chromosomes in the GnomAD database, including 44,600 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 0.22 (3842 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40758 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=0.015335411).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.235A>G	p.Lys79Glu	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.235A>G	p.Lys79Glu	missense_variant	1/1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000703543.1	c.-125-23920A>G		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33972 AN: 152016 Hom.: 3840 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.227 AC: 56455 AN: 249032 Hom.: 6554 AF XY: 0.224 AC XY: 30310 AN XY: 135148

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.234 AC: 342482 AN: 1461344 Hom.: 40758 Cov.: 53 AF XY: 0.233 AC XY: 169067 AN XY: 726942

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.223 AC: 33985 AN: 152134 Hom.: 3842 Cov.: 32 AF XY: 0.226 AC XY: 16768 AN XY: 74358

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.213

Alfa AF: 0.228 Hom.: 7519

Bravo AF: 0.217

TwinsUK AF: 0.236 AC: 876

ALSPAC AF: 0.249 AC: 959

ESP6500AA AF: 0.206 AC: 889

ESP6500EA AF: 0.228 AC: 1950

ExAC AF: 0.225 AC: 27293

Asia WGS AF: 0.241 AC: 838 AN: 3478

EpiCase AF: 0.223

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0040
DANN	Benign	0.46
DEOGEN2	Benign	0.00086	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0023	N
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.0080
MPC		0.027
ClinPred		0.00058	T
GERP RS		-4.2
Varity_R		0.048
gMVP		0.031

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: rs7135018; hg19: chr12-11150240; COSMIC: COSV67860971;