rs12578654

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_176888.2(TAS2R19):c.317G>A(p.Cys106Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.015 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAS2R19
NM_176888.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.746

Publications

2 publications found

Variant links:

Genes affected

TAS2R19 (HGNC:19108): (taste 2 receptor member 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of taste. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TAS2R19 links:

ENSG00000275778 (HGNC:):

ENSG00000275778 links:

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]

PRH1 links:

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]

PRR4 links:

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]

TAS2R14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008672774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R19	NM_176888.2 link	c.317G>A	p.Cys106Tyr	missense_variant	Exon 1 of 1	ENST00000390673.2	NP_795369.1	P59542

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R19	ENST00000390673.2 link	c.317G>A	p.Cys106Tyr	missense_variant	Exon 1 of 1	6	NM_176888.2	ENSP00000375091.2		P59542
ENSG00000275778	ENST00000536668.2 link	n.109+12527G>A		intron_variant	Intron 3 of 9	5		ENSP00000482961.1		A0A087WZY1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

1421

AN:

93532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00575

Gnomad AMI

AF:

0.0182

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.0352

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251022

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111742

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0152

AC:

1423

AN:

93674

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

743

AN XY:

45954

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00573

AC:

182

AN:

31774

American (AMR)

AF:

0.0229

AC:

200

AN:

8750

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

1912

East Asian (EAS)

AF:

0.0352

AC:

AN:

2616

South Asian (SAS)

AF:

0.0254

AC:

AN:

2596

European-Finnish (FIN)

AF:

0.0224

AC:

137

AN:

6120

Middle Eastern (MID)

AF:

0.0352

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.0176

AC:

669

AN:

38002

Other (OTH)

AF:

0.0244

AC:

AN:

1268

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.240

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0479

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.23

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.019

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0020

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-3.4

PhyloP100

0.75

PrimateAI

Benign

0.42

PROVEAN

Benign

8.7

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MutPred

0.63

Loss of catalytic residue at L107 (P = 0.0317);

MVP

0.14

MPC

0.0075

ClinPred

0.021

GERP RS

1.3

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.039

gMVP

0.28

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over