12-10806611-A-C

Variant names:

• chr12-10806611-A-C
• rs147209838
• NM_023918.3:c.370T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_023918.3(TAS2R8):​c.370T>G​(p.Trp124Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,948 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (4 hom.)
• Consequence: TAS2R8 NM_023918.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

TAS2R8 (HGNC:14915): (taste 2 receptor member 8) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023238689).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R8	NM_023918.3	c.370T>G	p.Trp124Gly	missense_variant	Exon 1 of 1	ENST00000240615.3	NP_076407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R8	ENST00000240615.3	c.370T>G	p.Trp124Gly	missense_variant	Exon 1 of 1	6	NM_023918.3	ENSP00000240615.2

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 133 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000706 AC: 177 AN: 250538 Hom.: 0 AF XY: 0.000731 AC XY: 99 AN XY: 135386

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.00140 AC: 2039 AN: 1461616 Hom.: 4 Cov.: 33 AF XY: 0.00135 AC XY: 978 AN XY: 727104

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.000873 AC: 133 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74482

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.000846

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000725 AC: 88

EpiCase AF: 0.00196

EpiControl AF: 0.00136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.8
DANN	Benign	0.62
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.075	N
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Benign	0.15
Sift	Benign	0.48	T
Sift4G	Benign	0.090	T
Polyphen		0.0070	B
Vest4		0.33
MVP		0.040
MPC		0.0020
ClinPred		0.027	T
GERP RS		-3.5
Varity_R		0.20
gMVP		0.049

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs147209838; hg19: chr12-10959210;