12-10938833-C-T

Variant names:

• chr12-10938833-C-T
• rs3741843
• NM_023922.2:c.375G>A

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.375G>A​(p.Arg125Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,613,234 control chromosomes in the GnomAD database, including 564,470 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 0.77 (46280 hom., cov: 32)
  • Exomes 𝑓: 0.84 (518190 hom.)
• Consequence: TAS2R14 NM_023922.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 36 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=-0.77).
• BP7: Synonymous conserved (PhyloP=0.297 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R14	NM_023922.2	c.375G>A	p.Arg125Arg	synonymous_variant	Exon 1 of 1	ENST00000537503.2	NP_076411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R14	ENST00000537503.2	c.375G>A	p.Arg125Arg	synonymous_variant	Exon 1 of 1	6	NM_023922.2	ENSP00000441949.1
ENSG00000275778	ENST00000536668.2	n.176+34822G>A		intron_variant	Intron 4 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116542 AN: 151966 Hom.: 46268 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.781

GnomAD2 exomes AF: 0.849 AC: 212389 AN: 250028 AF XY: 0.854

Gnomad AFR exome AF: 0.533

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.844

Gnomad EAS exome AF: 0.937

Gnomad FIN exome AF: 0.923

Gnomad NFE exome AF: 0.848

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.840 AC: 1227716 AN: 1461150 Hom.: 518190 Cov.: 56 AF XY: 0.842 AC XY: 611973 AN XY: 726872

African (AFR) AF: 0.534 AC: 17859 AN: 33444

American (AMR) AF: 0.887 AC: 39589 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 22144 AN: 26122

East Asian (EAS) AF: 0.955 AC: 37915 AN: 39692

South Asian (SAS) AF: 0.864 AC: 74454 AN: 86190

European-Finnish (FIN) AF: 0.920 AC: 48821 AN: 53084

Middle Eastern (MID) AF: 0.857 AC: 4944 AN: 5766

European-Non Finnish (NFE) AF: 0.838 AC: 931697 AN: 1111826

Other (OTH) AF: 0.833 AC: 50293 AN: 60378

GnomAD4 genome AF: 0.767 AC: 116580 AN: 152084 Hom.: 46280 Cov.: 32 AF XY: 0.775 AC XY: 57592 AN XY: 74342

African (AFR) AF: 0.535 AC: 22179 AN: 41436

American (AMR) AF: 0.831 AC: 12700 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4843 AN: 5176

South Asian (SAS) AF: 0.859 AC: 4147 AN: 4826

European-Finnish (FIN) AF: 0.924 AC: 9796 AN: 10600

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57296 AN: 67986

Other (OTH) AF: 0.783 AC: 1650 AN: 2108

Alfa AF: 0.824 Hom.: 83650

Bravo AF: 0.751

Asia WGS AF: 0.893 AC: 3102 AN: 3478

EpiCase AF: 0.843

EpiControl AF: 0.841

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		0.30
PromoterAI		-0.0049	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3741843; hg19: chr12-11091432; COSMIC: COSV108234658;