NM_023920.2:c.391C>T

Variant names:

• chr12-10908908-G-A
• rs142394171
• NM_023920.2:c.391C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

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 -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023920.2. 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
	TAS2R13	NM_023920.2	MANE Select	c.391C>T	p.Leu131Leu	synonymous	Exon 1 of 1	NP_076409.1	Q9NYV9
	PRH1	NM_001291315.2		c.104-25812C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-58-24633C>T		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R13	ENST00000390677.2	TSL:6 MANE Select	c.391C>T	p.Leu131Leu	synonymous	Exon 1 of 1	ENSP00000375095.2	Q9NYV9
	ENSG00000275778	ENST00000536668.2	TSL:5	n.177-24633C>T		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-58-24633C>T		intron	N/A	ENSP00000515364.1	A0A087WYT0

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

GnomAD2 exomes AF: 0.00489 AC: 1220 AN: 249356 AF XY: 0.00546

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 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

African (AFR) AF: 0.000898 AC: 30 AN: 33396

American (AMR) AF: 0.00298 AC: 133 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 56 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.0109 AC: 942 AN: 86180

European-Finnish (FIN) AF: 0.00306 AC: 161 AN: 52636

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5766

European-Non Finnish (NFE) AF: 0.00465 AC: 5170 AN: 1111866

Other (OTH) AF: 0.00452 AC: 273 AN: 60362

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

African (AFR) AF: 0.000963 AC: 40 AN: 41558

American (AMR) AF: 0.00308 AC: 47 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4818

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 68010

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00352

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00611

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism

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: rs142394171; hg19: chr12-11061507;