1-1331708-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152228.3(TAS1R3):c.262G>A(p.Asp88Asn) 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 benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.54

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16196567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS1R3	NM_152228.3	c.262G>A	p.Asp88Asn	missense_variant	2/6	ENST00000339381.6
TAS1R3	XM_017002435.2	c.262G>A	p.Asp88Asn	missense_variant	2/5
TAS1R3	XM_017002436.2	c.262G>A	p.Asp88Asn	missense_variant	2/5
TAS1R3	XM_047431571.1	c.262G>A	p.Asp88Asn	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R3	ENST00000339381.6	c.262G>A	p.Asp88Asn	missense_variant	2/6	2	NM_152228.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2023

The c.262G>A (p.D88N) alteration is located in exon 2 (coding exon 2) of the TAS1R3 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the aspartic acid (D) at amino acid position 88 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	1.1
Dann	Benign	0.86
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.14
Sift	Benign	0.48	T
Sift4G	Benign	0.47	T
Polyphen		0.20	B
Vest4		0.13
MutPred		0.44		Gain of methylation at K86 (P = 0.0907);
MVP		0.47
ClinPred		0.20	T
GERP RS		-1.7
Varity_R		0.039
gMVP		0.34

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: rs867182117; hg19: chr1-1267088;