chr12-10998285-G-A

Variant names:

• chr12-10998285-G-A
• rs7301234
• NM_176889.4:c.-410C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176889.4(TAS2R20):​c.-410C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,902 control chromosomes in the GnomAD database, including 8,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8925 hom., cov: 32)
• Consequence: TAS2R20 NM_176889.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 8 publications found

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]

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 (BayesDel_noAF=-1.04).
• 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 rank	MANE	Protein	UniProt
TAS2R20	NM_176889.4	c.-410C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000538986.2	NP_795370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R20	ENST00000538986.2	c.-410C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_176889.4	ENSP00000441624.1
ENSG00000275778	ENST00000536668.2	n.110-24564C>T		intron_variant	Intron 3 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46306 AN: 151784 Hom.: 8922 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46319 AN: 151902 Hom.: 8925 Cov.: 32 AF XY: 0.315 AC XY: 23376 AN XY: 74218

African (AFR) AF: 0.106 AC: 4414 AN: 41478

American (AMR) AF: 0.394 AC: 5992 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3466

East Asian (EAS) AF: 0.736 AC: 3795 AN: 5154

South Asian (SAS) AF: 0.623 AC: 2999 AN: 4812

European-Finnish (FIN) AF: 0.329 AC: 3476 AN: 10554

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22677 AN: 67910

Other (OTH) AF: 0.363 AC: 766 AN: 2112

Alfa AF: 0.293 Hom.: 962

Bravo AF: 0.301

Asia WGS AF: 0.608 AC: 2101 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.16
PhyloP100		0.075
PromoterAI		-0.0065	Neutral

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

Other links and lift over

dbSNP: rs7301234; hg19: chr12-11150884;