NM_152228.3:c.2494G>A

Variant names:

• chr1-1334399-G-A
• rs35913253
• NM_152228.3:c.2494G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152228.3(TAS1R3):​c.2494G>A​(p.Gly832Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

Genes affected

TAS1R3 (HGNC:15661): (taste 1 receptor member 3) The protein encoded by this gene is a G-protein coupled receptor involved in taste responses. The encoded protein can form a heterodimeric receptor with TAS1R1 to elicit the umami taste response, or it can bind with TAS1R2 to form a receptor for the sweet taste response. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040351123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R3	NM_152228.3	c.2494G>A	p.Gly832Arg	missense_variant	Exon 6 of 6	ENST00000339381.6	NP_689414.2
TAS1R3	XM_017002435.2	c.2620G>A	p.Gly874Arg	missense_variant	Exon 5 of 5		XP_016857924.1
TAS1R3	XM_017002436.2	c.2617G>A	p.Gly873Arg	missense_variant	Exon 5 of 5		XP_016857925.1
TAS1R3	XM_047431571.1	c.2491G>A	p.Gly831Arg	missense_variant	Exon 6 of 6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6	c.2494G>A	p.Gly832Arg	missense_variant	Exon 6 of 6	2	NM_152228.3	ENSP00000344411.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000833 AC: 2 AN: 240228 Hom.: 0 AF XY: 0.00000763 AC XY: 1 AN XY: 131096

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454160 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.1
DANN	Benign	0.69
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.18
Sift	Benign	0.59	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.37		Loss of relative solvent accessibility (P = 0.0676);
MVP		0.30
ClinPred		0.031	T
GERP RS		-1.5
Varity_R		0.038
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs35913253; hg19: chr1-1269779;