Variant 1-1332039-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152228.3(TAS1R3):c.508A>T(p.Ser170Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TAS1R3
NM_152228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

TAS1R3 (HGNC:15661): (taste 1 receptor member 3) The protein encoded by this gene is a G-protein coupled receptor involved in taste responses. The encoded protein can form a heterodimeric receptor with TAS1R1 to elicit the umami taste response, or it can bind with TAS1R2 to form a receptor for the sweet taste response. [provided by RefSeq, Nov 2015]

TAS1R3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAS1R3	NM_152228.3 linkuse as main transcript	c.508A>T	p.Ser170Cys	missense_variant	3/6	ENST00000339381.6	NP_689414.2
TAS1R3	XM_017002435.2 linkuse as main transcript	c.508A>T	p.Ser170Cys	missense_variant	3/5		XP_016857924.1
TAS1R3	XM_017002436.2 linkuse as main transcript	c.508A>T	p.Ser170Cys	missense_variant	3/5		XP_016857925.1
TAS1R3	XM_047431571.1 linkuse as main transcript	c.508A>T	p.Ser170Cys	missense_variant	3/6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6 linkuse as main transcript	c.508A>T	p.Ser170Cys	missense_variant	3/6	2	NM_152228.3	ENSP00000344411	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241738

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132524

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:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455628

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724338

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

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

Oct 17, 2023

The c.508A>T (p.S170C) alteration is located in exon 3 (coding exon 3) of the TAS1R3 gene. This alteration results from a A to T substitution at nucleotide position 508, causing the serine (S) at amino acid position 170 to be replaced by a cysteine (C). 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

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.71

Eigen

Benign

0.16

Eigen_PC

Benign

0.0075

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.65

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.42

MutPred

0.80

Loss of disorder (P = 0.013);

MVP

0.74

ClinPred

0.80

GERP RS

2.2

Varity_R

0.34

gMVP

0.82

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