12-10939019-G-A

Position:

• chr12-10939019-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_023922.2(TAS2R14):​c.189C>T​(p.Phe63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,613,458 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (50 hom.)
• Consequence: TAS2R14 NM_023922.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.62

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 12-10939019-G-A is Benign according to our data. Variant chr12-10939019-G-A is described in ClinVar as [Benign]. Clinvar id is 719366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.62 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R14	NM_023922.2	c.189C>T	p.Phe63=	synonymous_variant	1/1	ENST00000537503.2	NP_076411.1
PRH1-TAS2R14	NM_001316893.2	c.208-442C>T		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.544+34636C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R14	ENST00000537503.2	c.189C>T	p.Phe63=	synonymous_variant	1/1		NM_023922.2	ENSP00000441949	P1
	ENST00000703543.1	c.-59+34636C>T		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152152 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00829

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00497 AC: 1242 AN: 249968 Hom.: 8 AF XY: 0.00481 AC XY: 650 AN XY: 135072

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000905

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00135

Gnomad FIN exome AF: 0.00330

Gnomad NFE exome AF: 0.00942

Gnomad OTH exome AF: 0.00411

GnomAD4 exome AF: 0.00724 AC: 10581 AN: 1461188 Hom.: 50 Cov.: 36 AF XY: 0.00700 AC XY: 5089 AN XY: 726826

Gnomad4 AFR exome AF: 0.000628

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00384

Gnomad4 NFE exome AF: 0.00887

Gnomad4 OTH exome AF: 0.00524

GnomAD4 genome AF: 0.00458 AC: 698 AN: 152270 Hom.: 3 Cov.: 32 AF XY: 0.00393 AC XY: 293 AN XY: 74476

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00831

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00669 Hom.: 2

Bravo AF: 0.00417

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00813

EpiControl AF: 0.00701

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142263768; hg19: chr12-11091618;