dbSNP rs373171619: TAS1R1:p.Asn69Thr (chr1-6570923-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138697.4(TAS1R1):c.206A>C(p.Asn69Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N69S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34726673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4 link	c.206A>C	p.Asn69Thr	missense_variant	Exon 2 of 6	ENST00000333172.11	NP_619642.2	Q7RTX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAS1R1	ENST00000333172.11 link	c.206A>C	p.Asn69Thr	missense_variant	Exon 2 of 6	1	NM_138697.4	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000351136.7 link	c.206A>C	p.Asn69Thr	missense_variant	Exon 2 of 5	2		ENSP00000312558.5	Q7RTX1-2
TAS1R1	ENST00000415267.1 link	c.-20A>C		upstream_gene_variant		1		ENSP00000408448.1	H0Y6X0
TAS1R1	ENST00000411823.5 link	c.-20A>C		upstream_gene_variant		2		ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.0086

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

0.089

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.025

D;T

Sift4G

Uncertain

0.049

D;D

Polyphen

0.99

D;P

Vest4

0.42

MutPred

0.45

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.72

MPC

0.56

ClinPred

0.87

GERP RS

4.0

Varity_R

0.12

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over