Genetic Variant TAS1R1:p.Asn69Ile (chr1-6570923-A-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_138697.4(TAS1R1):c.206A>T(p.Asn69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,450,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TAS1R1
NM_138697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.206A>T	p.Asn69Ile	missense	Exon 2 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.206A>T	p.Asn69Ile	missense	Exon 2 of 5	NP_803884.1	Q7RTX1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.206A>T	p.Asn69Ile	missense	Exon 2 of 6	ENSP00000331867.6	Q7RTX1-1
TAS1R1	ENST00000351136.7	TSL:2	c.206A>T	p.Asn69Ile	missense	Exon 2 of 5	ENSP00000312558.5	Q7RTX1-2
TAS1R1	ENST00000415267.1	TSL:1	c.-20A>T		upstream_gene	N/A	ENSP00000408448.1	H0Y6X0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000965

AC:

AN:

1450892

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

720898

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24968

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

83764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1106510

Other (OTH)

AF:

0.00

AC:

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

2.0

PhyloP100

1.5

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.66

MutPred

0.56

Gain of catalytic residue at N69 (P = 0.1052)

MVP

0.80

MPC

0.74

ClinPred

0.98

GERP RS

4.0

PromoterAI

0.0036

Neutral

(source)

Varity_R

0.46

gMVP

0.67

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over