rs12578654

Variant names:

• chr12-11022255-C-T
• rs12578654
• NM_176888.2:c.317G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_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. 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 0.015 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R19 NM_176888.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746

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]

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• 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	c.317G>A	p.Cys106Tyr	missense_variant	Exon 1 of 1	ENST00000390673.2	NP_795369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R19	ENST00000390673.2	c.317G>A	p.Cys106Tyr	missense_variant	Exon 1 of 1	6	NM_176888.2	ENSP00000375091.2
ENSG00000275778	ENST00000703543.1	c.-126+24765G>A		intron_variant	Intron 1 of 3			ENSP00000515364.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1421 AN: 93532 Hom.: 0 Cov.: 33 FAILED QC

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

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 251022 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135824

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 SAS 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: 1 AN: 1461502 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727048

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0152 AC: 1423 AN: 93674 Hom.: 0 Cov.: 33 AF XY: 0.0162 AC XY: 743 AN XY: 45954

Gnomad4 AFR AF: 0.00573

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0244

Alfa AF: 0.0479 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.23
DANN	Benign	0.41
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0020	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-3.4	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	8.7	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.63		Loss of catalytic residue at L107 (P = 0.0317);
MVP		0.14
MPC		0.0075
ClinPred		0.021	T
GERP RS		1.3
Varity_R		0.039
gMVP		0.28

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: rs12578654; hg19: chr12-11174854;