chr12-10997121-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]

PRH1-TAS2R14 (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]

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

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
PRH1-TAS2R14	NM_001316893.2	c.141-23400T>C		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.478-23400T>C		intron_variant, non_coding_transcript_variant

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		NM_176889.4	ENSP00000441624	P1
	ENST00000703543.1	c.-125-23400T>C		intron_variant				ENSP00000515364	P1

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
MutationTaster	Benign	1.0	P
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;