12-11133334-C-T

Position:

• chr12-11133334-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001097643.2(TAS2R30):​c.911G>A​(p.Arg304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TAS2R30 NM_001097643.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.711

Genes affected

TAS2R30 (HGNC:19112): (taste 2 receptor member 30) Enables bitter taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of bitter taste. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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-TAS2R14 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060048044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R30	NM_001097643.2	c.911G>A	p.Arg304Lys	missense_variant	1/1	ENST00000539585.1	NP_001091112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R30	ENST00000539585.1	c.911G>A	p.Arg304Lys	missense_variant	1/1	6	NM_001097643.2	ENSP00000444736.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.911G>A (p.R304K) alteration is located in exon 1 (coding exon 1) of the TAS2R30 gene. This alteration results from a G to A substitution at nucleotide position 911, causing the arginine (R) at amino acid position 304 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.3
DANN	Benign	0.75
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.0070
Sift	Benign	0.69	T
Sift4G	Benign	0.57	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.43		Gain of methylation at K302 (P = 0.1551);
MVP		0.030
MPC		0.0051
ClinPred		0.069	T
GERP RS		-3.3
Varity_R		0.056
gMVP		0.062

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: rs1946429904; hg19: chr12-11285933;