12-11186903-A-G

Variant names:

• chr12-11186903-A-G
• NM_181429.2:c.35T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_181429.2(TAS2R42):​c.35T>C​(p.Leu12Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAS2R42 NM_181429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R42	NM_181429.2	MANE Select	c.35T>C	p.Leu12Pro	missense	Exon 1 of 1	NP_852094.2	Q7RTR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R42	ENST00000334266.1	TSL:6 MANE Select	c.35T>C	p.Leu12Pro	missense	Exon 1 of 1	ENSP00000334050.1	Q7RTR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.088	N
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.99	T
PhyloP100		4.5
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.014	D
Vest4		0.69
MutPred		0.65		Gain of catalytic residue at A13 (P = 5e-04)
MVP		0.17
MPC		0.31
ClinPred		0.80	D
GERP RS		2.0
PromoterAI		0.0094	Neutral
gMVP		0.44
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr12-11339509;