12-11186351-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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: 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
• 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: Benign. The variant received -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.

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>C	p.Phe196Ser	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>C	p.Phe196Ser	missense	Exon 1 of 1	ENSP00000334050.1	Q7RTR8

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

GnomAD2 exomes AF: 0.610 AC: 152222 AN: 249664 AF XY: 0.616

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 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

African (AFR) AF: 0.207 AC: 6936 AN: 33434

American (AMR) AF: 0.634 AC: 28345 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 17067 AN: 26122

East Asian (EAS) AF: 0.752 AC: 29845 AN: 39690

South Asian (SAS) AF: 0.653 AC: 56271 AN: 86194

European-Finnish (FIN) AF: 0.665 AC: 35521 AN: 53392

Middle Eastern (MID) AF: 0.646 AC: 3723 AN: 5762

European-Non Finnish (NFE) AF: 0.590 AC: 654585 AN: 1109904

Other (OTH) AF: 0.591 AC: 35615 AN: 60308

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

African (AFR) AF: 0.222 AC: 9204 AN: 41488

American (AMR) AF: 0.596 AC: 9102 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3468

East Asian (EAS) AF: 0.743 AC: 3826 AN: 5152

South Asian (SAS) AF: 0.648 AC: 3116 AN: 4810

European-Finnish (FIN) AF: 0.666 AC: 7056 AN: 10598

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40546 AN: 67958

Other (OTH) AF: 0.546 AC: 1156 AN: 2116

Alfa AF: 0.575 Hom.: 58225

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
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
PhyloP100		0.29
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5020531; hg19: chr12-11338957; COSMIC: COSV107392110;