Genetic Variant TAS1R3:p.Leu93Pro (chr1-1331724-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152228.3(TAS1R3):c.278T>C(p.Leu93Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,600 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: 6.8e-7 ( 0 hom. )

Consequence

TAS1R3
NM_152228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R3	NM_152228.3 link	c.278T>C	p.Leu93Pro	missense_variant	Exon 2 of 6	ENST00000339381.6	NP_689414.2	Q7RTX0
TAS1R3	XM_017002435.2 link	c.278T>C	p.Leu93Pro	missense_variant	Exon 2 of 5		XP_016857924.1
TAS1R3	XM_017002436.2 link	c.278T>C	p.Leu93Pro	missense_variant	Exon 2 of 5		XP_016857925.1
TAS1R3	XM_047431571.1 link	c.278T>C	p.Leu93Pro	missense_variant	Exon 2 of 6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6 link	c.278T>C	p.Leu93Pro	missense_variant	Exon 2 of 6	2	NM_152228.3	ENSP00000344411.5		Q7RTX0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460600

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726580

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.278T>C (p.L93P) alteration is located in exon 2 (coding exon 2) of the TAS1R3 gene. This alteration results from a T to C substitution at nucleotide position 278, causing the leucine (L) at amino acid position 93 to be replaced by a proline (P). 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

0.57

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Benign

0.12

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

-0.034

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.49

MutPred

0.80

Loss of stability (P = 0.0023);

MVP

0.39

ClinPred

0.97

GERP RS

3.9

Varity_R

0.79

gMVP

0.88

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over