rs35969491

Positions:

• chr12-11186414-T-A
• chr12-11186414-T-C
• chr12-11186414-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181429.2(TAS2R42):​c.524A>T​(p.Tyr175Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,600,074 control chromosomes in the GnomAD database, including 281,843 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (22034 hom., cov: 32)
  • Exomes 𝑓: 0.59 (259809 hom.)
• Consequence: TAS2R42 NM_181429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9399787E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R42	NM_181429.2	c.524A>T	p.Tyr175Phe	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.524A>T	p.Tyr175Phe	missense_variant	1/1	6	NM_181429.2	ENSP00000334050.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77067 AN: 151924 Hom.: 22030 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.610 AC: 150197 AN: 246358 Hom.: 47337 AF XY: 0.616 AC XY: 82509 AN XY: 133902

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.753

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.671

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.594 AC: 860515 AN: 1448030 Hom.: 259809 Cov.: 39 AF XY: 0.597 AC XY: 430703 AN XY: 721112

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.507 AC: 77078 AN: 152044 Hom.: 22034 Cov.: 32 AF XY: 0.515 AC XY: 38259 AN XY: 74338

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.546

Alfa AF: 0.583 Hom.: 18668

Bravo AF: 0.491

TwinsUK AF: 0.590 AC: 2189

ALSPAC AF: 0.582 AC: 2243

ESP6500AA AF: 0.214 AC: 926

ESP6500EA AF: 0.595 AC: 5079

ExAC AF: 0.600 AC: 72657

Asia WGS AF: 0.651 AC: 2260 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.93
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.078	N
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.063
Sift	Benign	0.099	T
Sift4G	Benign	0.074	T
Vest4		0.081
MPC		0.047
ClinPred		0.025	T
GERP RS		1.5
gMVP		0.078

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: rs35969491; hg19: chr12-11339020; COSMIC: COSV62084971;