Variant chr1-6555563-A-G details in Genebe, Genetics Data Aggregator

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

Variant links:

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]

TAS1R1 links:

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ACMG classification

Classification made for transcript

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
TAS1R1	NM_138697.4 linkuse as main transcript	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6	ENST00000333172.11	NP_619642.2
TAS1R1	NM_177540.3 linkuse as main transcript	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/5		NP_803884.1
TAS1R1	XM_011542206.3 linkuse as main transcript	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6		XP_011540508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11 linkuse as main transcript	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/6	1	NM_138697.4	ENSP00000331867	P1	Q7RTX1-1
TAS1R1	ENST00000351136.7 linkuse as main transcript	c.190A>G	p.Arg64Gly	missense_variant, splice_region_variant	1/5	2		ENSP00000312558		Q7RTX1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000431

AC:

AN:

1392244

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

685078

show subpopulations

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

T;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

0.18

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.67

D;D;N

PrimateAI

Benign

0.44

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over