12-10997121-A-G

Position:

• chr12-10997121-A-G

Variant summary

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

The NM_176889.4(TAS2R20):​c.755T>C​(p.Phe252Ser) 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 1,613,084 control chromosomes in the GnomAD database, including 113,665 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 (8852 hom., cov: 32)
  • Exomes 𝑓: 0.36 (104813 hom.)
• Consequence: TAS2R20 NM_176889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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=1.8801835E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.755T>C	p.Phe252Ser	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.755T>C	p.Phe252Ser	missense_variant	1/1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000703543.1	c.-125-23400T>C		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46182 AN: 151858 Hom.: 8848 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.416 AC: 104425 AN: 251004 Hom.: 24946 AF XY: 0.430 AC XY: 58359 AN XY: 135652

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.361 AC: 527938 AN: 1461108 Hom.: 104813 Cov.: 52 AF XY: 0.371 AC XY: 269340 AN XY: 726882

Gnomad4 AFR exome AF: 0.0976

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: 0.304 AC: 46197 AN: 151976 Hom.: 8852 Cov.: 32 AF XY: 0.314 AC XY: 23304 AN XY: 74246

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.363

Alfa AF: 0.352 Hom.: 15410

Bravo AF: 0.301

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.317 AC: 1220

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.351 AC: 3016

ExAC AF: 0.411 AC: 49914

Asia WGS AF: 0.609 AC: 2110 AN: 3476

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	0.078
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.16
DANN	Benign	0.33
DEOGEN2	Benign	0.00049	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00064	N
MetaRNN	Benign	0.0000019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.0010
Sift	Benign	0.40	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.030
ClinPred		0.0049	T
GERP RS		-2.3
Varity_R		0.056
gMVP		0.043

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: rs10845280; hg19: chr12-11149720; COSMIC: COSV67856040;