12-10908908-G-A

Position:

• chr12-10908908-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_023920.2(TAS2R13):​c.391C>T​(p.Leu131Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,612,860 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (37 hom.)
• Consequence: TAS2R13 NM_023920.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.541

Genes affected

TAS2R13 (HGNC:14919): (taste 2 receptor member 13) 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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-10908908-G-A is Benign according to our data. Variant chr12-10908908-G-A is described in ClinVar as [Benign]. Clinvar id is 710271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.541 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
TAS2R13	NM_023920.2	c.391C>T	p.Leu131Leu	synonymous_variant	1/1	ENST00000390677.2	NP_076409.1
PRH1	NM_001291315.2	c.104-25812C>T		intron_variant			NP_001278244.1
PRH1	NM_001291314.2	c.-58-24633C>T		intron_variant			NP_001278243.1
PRH1-PRR4	NR_037918.2	n.545-24633C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R13	ENST00000390677.2	c.391C>T	p.Leu131Leu	synonymous_variant	1/1	6	NM_023920.2	ENSP00000375095.2
ENSG00000275778	ENST00000703543.1	c.-58-24633C>T		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152130 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00489 AC: 1220 AN: 249356 Hom.: 6 AF XY: 0.00546 AC XY: 737 AN XY: 134888

Gnomad AFR exome AF: 0.000870

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.00407

Gnomad NFE exome AF: 0.00554

Gnomad OTH exome AF: 0.00709

GnomAD4 exome AF: 0.00468 AC: 6832 AN: 1460612 Hom.: 37 Cov.: 33 AF XY: 0.00505 AC XY: 3667 AN XY: 726614

Gnomad4 AFR exome AF: 0.000898

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00306

Gnomad4 NFE exome AF: 0.00465

Gnomad4 OTH exome AF: 0.00452

GnomAD4 genome AF: 0.00374 AC: 569 AN: 152248 Hom.: 3 Cov.: 32 AF XY: 0.00387 AC XY: 288 AN XY: 74468

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00310 Hom.: 0

Bravo AF: 0.00352

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00611

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	Dec 31, 2019	- -
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	-0.79
CADD	Benign	1.7
DANN	Benign	0.83

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: rs142394171; hg19: chr12-11061507;