chr12-10806806-T-A

Variant names:

• chr12-10806806-T-A
• rs184824661
• NM_023918.3:c.175A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_023918.3(TAS2R8):​c.175A>T​(p.Ile59Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: TAS2R8 NM_023918.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019144148).

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.175A>T	p.Ile59Phe	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.175A>T	p.Ile59Phe	missense	Exon 1 of 1	ENSP00000240615.2	Q9NYW2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 250758 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1461610 Hom.: 0 Cov.: 33 AF XY: 0.0000880 AC XY: 64 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.000828 AC: 37 AN: 44684

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000953 AC: 106 AN: 1111870

Other (OTH) AF: 0.0000828 AC: 5 AN: 60376

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74460

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.000589 AC: 9 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000396 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.070
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.026	D
Polyphen		0.099	B
Vest4		0.15
MVP		0.048
MPC		0.0048
ClinPred		0.12	T
GERP RS		-2.9
PromoterAI		0.0019	Neutral
Varity_R		0.35
gMVP		0.075
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs184824661; hg19: chr12-10959405;