12-10908523-T-C

Variant names:

• chr12-10908523-T-C
• rs1015443
• NM_023920.2:c.776A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023920.2(TAS2R13):​c.776A>G​(p.Asn259Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,613,260 control chromosomes in the GnomAD database, including 266,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (20760 hom., cov: 32)
  • Exomes 𝑓: 0.58 (245806 hom.)
• Consequence: TAS2R13 NM_023920.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 60 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0256323E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R13	NM_023920.2	c.776A>G	p.Asn259Ser	missense_variant	Exon 1 of 1	ENST00000390677.2	NP_076409.1
PRH1	NM_001291315.2	c.104-25427A>G		intron_variant	Intron 3 of 5		NP_001278244.1
PRH1	NM_001291314.2	c.-58-24248A>G		intron_variant	Intron 3 of 6		NP_001278243.1
PRH1-PRR4	NR_037918.2	n.545-24248A>G		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R13	ENST00000390677.2	c.776A>G	p.Asn259Ser	missense_variant	Exon 1 of 1	6	NM_023920.2	ENSP00000375095.2
ENSG00000275778	ENST00000536668.2	n.177-24248A>G		intron_variant	Intron 4 of 9	5		ENSP00000482961.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74626 AN: 151884 Hom.: 20759 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.524

GnomAD2 exomes AF: 0.593 AC: 148554 AN: 250392 AF XY: 0.601

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.728

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.576 AC: 841547 AN: 1461254 Hom.: 245806 Cov.: 49 AF XY: 0.579 AC XY: 421131 AN XY: 726916

African (AFR) AF: 0.207 AC: 6910 AN: 33458

American (AMR) AF: 0.625 AC: 27900 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 16703 AN: 26124

East Asian (EAS) AF: 0.734 AC: 29106 AN: 39680

South Asian (SAS) AF: 0.649 AC: 55936 AN: 86232

European-Finnish (FIN) AF: 0.641 AC: 34212 AN: 53384

Middle Eastern (MID) AF: 0.633 AC: 3652 AN: 5768

European-Non Finnish (NFE) AF: 0.569 AC: 632471 AN: 1111602

Other (OTH) AF: 0.574 AC: 34657 AN: 60374

GnomAD4 genome AF: 0.491 AC: 74634 AN: 152006 Hom.: 20760 Cov.: 32 AF XY: 0.500 AC XY: 37111 AN XY: 74274

African (AFR) AF: 0.217 AC: 8993 AN: 41512

American (AMR) AF: 0.581 AC: 8854 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3705 AN: 5170

South Asian (SAS) AF: 0.642 AC: 3089 AN: 4814

European-Finnish (FIN) AF: 0.647 AC: 6830 AN: 10558

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38968 AN: 67918

Other (OTH) AF: 0.527 AC: 1114 AN: 2112

Alfa AF: 0.557 Hom.: 105875

Bravo AF: 0.476

TwinsUK AF: 0.568 AC: 2106

ALSPAC AF: 0.562 AC: 2167

ESP6500AA AF: 0.219 AC: 967

ESP6500EA AF: 0.582 AC: 5005

ExAC AF: 0.584 AC: 70901

Asia WGS AF: 0.638 AC: 2215 AN: 3478

EpiCase AF: 0.585

EpiControl AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.019
DANN	Benign	0.73
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0089	N
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.21	N
PhyloP100		-1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.018
Sift	Benign	0.37	T
Sift4G	Benign	0.29	T
Polyphen		0.040	B
Vest4		0.0080
MPC		0.015
ClinPred		0.020	T
GERP RS		0.22
Varity_R		0.044
gMVP		0.015
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: rs1015443; hg19: chr12-11061122; COSMIC: COSV104429662;