chr12-10806611-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. W124R) has been classified as Likely benign.

• 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023918.3. 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
	TAS2R8	NM_023918.3	MANE Select	c.370T>G	p.Trp124Gly	missense	Exon 1 of 1	NP_076407.1	Q9NYW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R8	ENST00000240615.3	TSL:6 MANE Select	c.370T>G	p.Trp124Gly	missense	Exon 1 of 1	ENSP00000240615.2	Q9NYW2

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

GnomAD2 exomes AF: 0.000706 AC: 177 AN: 250538 AF XY: 0.000731

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 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

African (AFR) AF: 0.000149 AC: 5 AN: 33468

American (AMR) AF: 0.000403 AC: 18 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53398

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00176 AC: 1955 AN: 1111892

Other (OTH) AF: 0.000911 AC: 55 AN: 60374

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

African (AFR) AF: 0.000361 AC: 15 AN: 41592

American (AMR) AF: 0.000327 AC: 5 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68018

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00127 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 v4.9

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
PhyloP100		-1.2
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs147209838; hg19: chr12-10959210;