12-11186351-A-G

Position:

• chr12-11186351-A-G

Variant summary

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

The NM_181429.2(TAS2R42):​c.587T>C​(p.Phe196Ser) 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 1,611,552 control chromosomes in the GnomAD database, including 283,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 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 (22040 hom., cov: 32)
  • Exomes 𝑓: 0.59 (261859 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.398781E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R42	NM_181429.2	c.587T>C	p.Phe196Ser	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>C	p.Phe196Ser	missense_variant	1/1		NM_181429.2	ENSP00000334050	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77080 AN: 151942 Hom.: 22036 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.647

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: 152222 AN: 249664 Hom.: 48018 AF XY: 0.616 AC XY: 83481 AN XY: 135432

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.753

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.672

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.595 AC: 867908 AN: 1459492 Hom.: 261859 Cov.: 48 AF XY: 0.598 AC XY: 433986 AN XY: 726162

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.653

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.507 AC: 77091 AN: 152060 Hom.: 22040 Cov.: 32 AF XY: 0.515 AC XY: 38258 AN XY: 74340

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.652

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: 0.596 Hom.: 39984

Bravo AF: 0.491

TwinsUK AF: 0.590 AC: 2189

ALSPAC AF: 0.582 AC: 2243

ESP6500AA AF: 0.219 AC: 962

ESP6500EA AF: 0.598 AC: 5138

ExAC AF: 0.600 AC: 72767

Asia WGS AF: 0.651 AC: 2261 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.11
Eigen	Benign	-2.1
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00043	N
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	5.5	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.024
MPC		0.062
ClinPred		0.0017	T
GERP RS		1.6
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;