7-143222182-G-C

Variant names:

• chr7-143222182-G-C
• rs1800243086
• NM_176882.2:c.104G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_176882.2(TAS2R40):​c.104G>C​(p.Gly35Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: not found (cov: 32)
• Consequence: TAS2R40 NM_176882.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

TAS2R40 (HGNC:18885): (taste 2 receptor member 40) This gene encodes a member of the bitter taste receptor family which belong to the G protein-coupled receptor superfamily and are predominantly expressed in taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a seven-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered together with eight other taste receptor genes on chromosome 7. A decrease in the expression of this gene is associated with hypogeusia. [provided by RefSeq, Jul 2017]

ENSG00000268170 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176882.2. 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
	TAS2R40	NM_176882.2	MANE Select	c.104G>C	p.Gly35Ala	missense	Exon 1 of 1	NP_795363.1	P59535

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R40	ENST00000408947.4	TSL:6 MANE Select	c.104G>C	p.Gly35Ala	missense	Exon 1 of 1	ENSP00000386210.3	P59535
	ENSG00000268170	ENST00000595842.2	TSL:6	n.86C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Polyphen		0.62	P
Vest4		0.52
MutPred		0.77		Gain of catalytic residue at G35 (P = 0.0483)
MVP		0.73
MPC		0.21
ClinPred		0.60	D
GERP RS		2.0
PromoterAI		-0.011	Neutral
Varity_R		0.13
gMVP		0.40
Mutation Taster		=80/20	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: rs1800243086; hg19: chr7-142919275;