12-11186351-A-T

Position:

• chr12-11186351-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181429.2(TAS2R42):​c.587T>A​(p.Phe196Tyr) 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. 13/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. F196S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAS2R42 NM_181429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

Genes affected

TAS2R42 (HGNC:18888): (taste 2 receptor member 42) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29530466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R42	NM_181429.2	c.587T>A	p.Phe196Tyr	missense_variant	1/1	ENST00000334266.1	NP_852094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R42	ENST00000334266.1	c.587T>A	p.Phe196Tyr	missense_variant	1/1		NM_181429.2	ENSP00000334050	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.32
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0099	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.027
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Vest4		0.13
MutPred		0.68		Gain of catalytic residue at F196 (P = 0.0068);
MVP		0.014
MPC		0.046
ClinPred		0.25	T
GERP RS		1.6
gMVP		0.17

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: rs5020531; hg19: chr12-11338957;