12-11186351-A-C

Variant names:

• chr12-11186351-A-C
• rs5020531
• NM_181429.2:c.587T>G

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.587T>G​(p.Phe196Cys) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAS2R42 NM_181429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 35 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=0.22577325).

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.587T>G	p.Phe196Cys	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.587T>G	p.Phe196Cys	missense	Exon 1 of 1	ENSP00000334050.1	Q7RTR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461108 Hom.: 0 Cov.: 48 AF XY: 0.00000138 AC XY: 1 AN XY: 726894

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111358

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.8
DANN	Benign	0.12
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0080	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.29
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.045
Sift	Benign	0.27	T
Sift4G	Benign	0.13	T
Vest4		0.16
MutPred		0.68		Gain of catalytic residue at T198 (P = 8e-04)
MVP		0.014
MPC		0.053
ClinPred		0.30	T
GERP RS		1.6
gMVP		0.24
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: rs5020531; hg19: chr12-11338957;