Variant 1-1331757-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152228.3(TAS1R3):c.311C>G(p.Ser104Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,550 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: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TAS1R3
NM_152228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.889

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAS1R3	NM_152228.3 linkuse as main transcript	c.311C>G	p.Ser104Trp	missense_variant	2/6	ENST00000339381.6	NP_689414.2
TAS1R3	XM_017002435.2 linkuse as main transcript	c.311C>G	p.Ser104Trp	missense_variant	2/5		XP_016857924.1
TAS1R3	XM_017002436.2 linkuse as main transcript	c.311C>G	p.Ser104Trp	missense_variant	2/5		XP_016857925.1
TAS1R3	XM_047431571.1 linkuse as main transcript	c.311C>G	p.Ser104Trp	missense_variant	2/6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6 linkuse as main transcript	c.311C>G	p.Ser104Trp	missense_variant	2/6	2	NM_152228.3	ENSP00000344411	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249672

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460550

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 19, 2024

The c.311C>G (p.S104W) alteration is located in exon 2 (coding exon 2) of the TAS1R3 gene. This alteration results from a C to G substitution at nucleotide position 311, causing the serine (S) at amino acid position 104 to be replaced by a tryptophan (W). 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

0.15

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.64

Eigen

Benign

0.00066

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.49

Sift

Benign

0.16

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.52

MutPred

0.67

Gain of catalytic residue at S104 (P = 0.0194);

MVP

0.64

ClinPred

0.50

GERP RS

3.0

Varity_R

0.20

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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