1-1331403-G-A

Position:

• chr1-1331403-G-A

Variant summary

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

The NM_152228.3(TAS1R3):​c.58G>A​(p.Gly20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R3	NM_152228.3	c.58G>A	p.Gly20Arg	missense_variant	1/6	ENST00000339381.6	NP_689414.2
TAS1R3	XM_017002435.2	c.58G>A	p.Gly20Arg	missense_variant	1/5		XP_016857924.1
TAS1R3	XM_017002436.2	c.58G>A	p.Gly20Arg	missense_variant	1/5		XP_016857925.1
TAS1R3	XM_047431571.1	c.58G>A	p.Gly20Arg	missense_variant	1/6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6	c.58G>A	p.Gly20Arg	missense_variant	1/6	2	NM_152228.3	ENSP00000344411	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722672

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 03, 2024

The c.58G>A (p.G20R) alteration is located in exon 1 (coding exon 1) of the TAS1R3 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the glycine (G) at amino acid position 20 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.63	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.046	D
Polyphen		0.79	P
Vest4		0.63
MutPred		0.47		Gain of solvent accessibility (P = 0.0097);
MVP		0.57
ClinPred		0.91	D
GERP RS		3.5
Varity_R		0.19
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1266783;