1-6555563-A-G

Variant summary

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

The NM_138697.4(TAS1R1):c.190A>G(p.Arg64Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,392,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense, splice_region
• Scores: Splicing: ADA: 0.8553
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

Genes affected

TAS1R1 (HGNC:14448): (taste 1 receptor member 1) The protein encoded by this gene is a G protein-coupled receptor and is a component of the heterodimeric amino acid taste receptor T1R1+3. The T1R1+3 receptor responds to L-amino acids but not to D-enantiomers or other compounds. Most amino acids that are perceived as sweet activate T1R1+3, and this activation is strictly dependent on an intact T1R1+3 heterodimer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

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	UniProt
TAS1R1	NM_138697.4	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6	ENST00000333172.11
TAS1R1	NM_177540.3	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/5
TAS1R1	XM_011542206.3	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS1R1	ENST00000333172.11	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6	1	NM_138697.4	P1
TAS1R1	ENST00000351136.7	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1392244 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 685078

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: 0.00000559

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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

Feb 26, 2024

The c.190A>G (p.R64G) alteration is located in exon 1 (coding exon 1) of the TAS1R1 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the arginine (R) at amino acid position 64 to be replaced by a glycine (G). 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	0.099
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	0.67	D;D;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.077	T;T
Polyphen		0.014	B;D
Vest4		0.65
MutPred		0.54		Loss of stability (P = 0.0832);Loss of stability (P = 0.0832);
MVP		0.68
MPC		0.22
ClinPred		0.53	D
GERP RS		2.9
Varity_R		0.16
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.86
dbscSNV1_RF	Benign	0.57
SpliceAI score (max)		0.17		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: rs1225972133; hg19: chr1-6615623;