12-11186930-G-T

Variant names:

• chr12-11186930-G-T
• rs752186513
• NM_181429.2:c.8C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181429.2(TAS2R42):​c.8C>A​(p.Thr3Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. T3I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TAS2R42 NM_181429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07353476).

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.8C>A	p.Thr3Asn	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.8C>A	p.Thr3Asn	missense	Exon 1 of 1	ENSP00000334050.1	Q7RTR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000817 AC: 2 AN: 244776 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457378 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 724234

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 86050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109138

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.37
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.027
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.024
Sift	Benign	0.51	T
Sift4G	Benign	0.56	T
Vest4		0.046
MutPred		0.32		Gain of catalytic residue at A2 (P = 0.0798)
MVP		0.014
MPC		0.046
ClinPred		0.026	T
GERP RS		-0.17
PromoterAI		-0.0064	Neutral
gMVP		0.046
Mutation Taster		=100/0	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

dbSNP: rs752186513; hg19: chr12-11339536;