NM_023922.2:c.114A>T

Variant names:

• chr12-10939094-T-A
• rs7138535
• NM_023922.2:c.114A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_023922.2(TAS2R14):​c.114A>T​(p.Gly38Gly) 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
• Publications: 28 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R14	NM_023922.2	MANE Select	c.114A>T	p.Gly38Gly	synonymous	Exon 1 of 1	NP_076411.1
	PRH1	NM_001291315.2		c.103+34561A>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-59+34561A>T		intron	N/A	NP_001278243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R14	ENST00000537503.2	TSL:6 MANE Select	c.114A>T	p.Gly38Gly	synonymous	Exon 1 of 1	ENSP00000441949.1
	ENSG00000275778	ENST00000536668.2	TSL:5	n.176+34561A>T		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.-59+34561A>T		intron	N/A	ENSP00000515364.1

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

GnomAD2 exomes AF: 0.243 AC: 60870 AN: 250642 AF XY: 0.238

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 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

African (AFR) AF: 0.219 AC: 7314 AN: 33462

American (AMR) AF: 0.297 AC: 13250 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4517 AN: 26122

East Asian (EAS) AF: 0.231 AC: 9165 AN: 39690

South Asian (SAS) AF: 0.184 AC: 15861 AN: 86208

European-Finnish (FIN) AF: 0.276 AC: 14708 AN: 53386

Middle Eastern (MID) AF: 0.184 AC: 1062 AN: 5766

European-Non Finnish (NFE) AF: 0.253 AC: 281765 AN: 1111726

Other (OTH) AF: 0.238 AC: 14348 AN: 60366

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

African (AFR) AF: 0.214 AC: 8891 AN: 41480

American (AMR) AF: 0.255 AC: 3903 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1190 AN: 5186

South Asian (SAS) AF: 0.186 AC: 899 AN: 4826

European-Finnish (FIN) AF: 0.274 AC: 2902 AN: 10578

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.254 AC: 17240 AN: 67974

Other (OTH) AF: 0.226 AC: 478 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		-1.1
PromoterAI		-0.0062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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