chr12-10908523-T-C

Position:

• chr12-10908523-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

(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 -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/exons	MANE	Protein	UniProt
TAS2R13	NM_023920.2	c.776A>G	p.Asn259Ser	missense_variant	1/1	ENST00000390677.2	NP_076409.1
PRH1-PRR4	NR_037918.2	n.545-24248A>G		intron_variant, non_coding_transcript_variant
PRH1	NM_001291314.2	c.-58-24248A>G		intron_variant			NP_001278243.1
PRH1	NM_001291315.2	c.104-25427A>G		intron_variant			NP_001278244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R13	ENST00000390677.2	c.776A>G	p.Asn259Ser	missense_variant	1/1		NM_023920.2	ENSP00000375095	P1
	ENST00000703543.1	c.-58-24248A>G		intron_variant				ENSP00000515364	P1

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

GnomAD3 exomes AF: 0.593 AC: 148554 AN: 250392 Hom.: 45611 AF XY: 0.601 AC XY: 81320 AN XY: 135318

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 SAS exome AF: 0.659

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

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.734

Gnomad4 SAS exome AF: 0.649

Gnomad4 FIN exome AF: 0.641

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.574

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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.527

Alfa AF: 0.572 Hom.: 55428

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
MutationTaster	Benign	1.0	P
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

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: rs1015443; hg19: chr12-11061122; COSMIC: COSV104429662;