rs7138535

Positions:

• chr12-10939094-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_023922.2(TAS2R14):​c.114A>T​(p.Gly38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,454 control chromosomes in the GnomAD database, including 49,909 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 0.24 (4418 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45491 hom.)
• Consequence: TAS2R14 NM_023922.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R14	NM_023922.2	c.114A>T	p.Gly38=	synonymous_variant	1/1	ENST00000537503.2	NP_076411.1
PRH1-TAS2R14	NM_001316893.2	c.208-517A>T		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.544+34561A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R14	ENST00000537503.2	c.114A>T	p.Gly38=	synonymous_variant	1/1		NM_023922.2	ENSP00000441949	P1
	ENST00000703543.1	c.-59+34561A>T		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36215 AN: 151988 Hom.: 4415 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.243 AC: 60870 AN: 250642 Hom.: 7638 AF XY: 0.238 AC XY: 32271 AN XY: 135542

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.248 AC: 361990 AN: 1461348 Hom.: 45491 Cov.: 35 AF XY: 0.245 AC XY: 178369 AN XY: 726958

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.238 AC: 36229 AN: 152106 Hom.: 4418 Cov.: 32 AF XY: 0.239 AC XY: 17777 AN XY: 74352

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.226

Alfa AF: 0.242 Hom.: 1505

Bravo AF: 0.235

Asia WGS AF: 0.235 AC: 818 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.73

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: rs7138535; hg19: chr12-11091693; COSMIC: COSV67860173;