Variant chr1-6570956-G-A 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.239G>A(p.Arg80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,028 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R80W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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:

LOC107984912 (HGNC:):

LOC107984912 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	UniProt
TAS1R1	NM_138697.4 link	c.239G>A	p.Arg80Gln	missense_variant	2/6	ENST00000333172.11	NP_619642.2	Q7RTX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAS1R1	ENST00000333172.11 link	c.239G>A	p.Arg80Gln	missense_variant	2/6	1	NM_138697.4	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000415267.1 link	c.14G>A	p.Arg5Gln	missense_variant	1/4	1		ENSP00000408448.1	H0Y6X0
TAS1R1	ENST00000351136.7 link	c.239G>A	p.Arg80Gln	missense_variant	2/5	2		ENSP00000312558.5	Q7RTX1-2
TAS1R1	ENST00000411823.5 link	c.14G>A	p.Arg5Gln	missense_variant	1/3	2		ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249690

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1460862

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000573

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Jan 26, 2022

The c.239G>A (p.R80Q) alteration is located in exon 2 (coding exon 2) of the TAS1R1 gene. This alteration results from a G to A substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 to be replaced by a glutamine (Q). 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

0.19

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.85

T;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.017

D;T

Polyphen

1.0

D;P

Vest4

0.58

MVP

0.74

MPC

0.52

ClinPred

0.87

GERP RS

4.2

Varity_R

0.65

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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