Genetic Variant NM_152228.3:c.2269T>C (chr1-1334174-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152228.3(TAS1R3):c.2269T>C(p.Cys757Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 1,594,094 control chromosomes in the GnomAD database, including 745,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.97 ( 71774 hom., cov: 35)

Exomes 𝑓: 0.97 ( 673937 hom. )

Consequence

TAS1R3
NM_152228.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.360

Publications

38 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3400132E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R3	NM_152228.3 link	c.2269T>C	p.Cys757Arg	missense_variant	Exon 6 of 6	ENST00000339381.6	NP_689414.2	Q7RTX0
TAS1R3	XM_017002435.2 link	c.2395T>C	p.Cys799Arg	missense_variant	Exon 5 of 5		XP_016857924.1
TAS1R3	XM_017002436.2 link	c.2392T>C	p.Cys798Arg	missense_variant	Exon 5 of 5		XP_016857925.1
TAS1R3	XM_047431571.1 link	c.2266T>C	p.Cys756Arg	missense_variant	Exon 6 of 6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6 link	c.2269T>C	p.Cys757Arg	missense_variant	Exon 6 of 6	2	NM_152228.3	ENSP00000344411.5		Q7RTX0

Frequencies

GnomAD3 genomes

AF:

0.970

AC:

147724

AN:

152236

Hom.:

71719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.988

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.980

Gnomad ASJ

AF:

0.977

Gnomad EAS

AF:

0.908

Gnomad SAS

AF:

0.915

Gnomad FIN

AF:

0.923

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.974

Gnomad OTH

AF:

0.967

GnomAD2 exomes

AF:

0.961

AC:

206771

AN:

215220

AF XY:

0.958

show subpopulations

Gnomad AFR exome

AF:

0.988

Gnomad AMR exome

AF:

0.988

Gnomad ASJ exome

AF:

0.983

Gnomad EAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.926

Gnomad NFE exome

AF:

0.973

Gnomad OTH exome

AF:

0.955

GnomAD4 exome

AF:

0.967

AC:

1393644

AN:

1441740

Hom.:

673937

Cov.:

104

AF XY:

0.965

AC XY:

690797

AN XY:

715638

show subpopulations

African (AFR)

AF:

0.988

AC:

32777

AN:

33176

American (AMR)

AF:

0.986

AC:

41075

AN:

41664

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

25249

AN:

25720

East Asian (EAS)

AF:

0.892

AC:

34483

AN:

38656

South Asian (SAS)

AF:

0.921

AC:

77293

AN:

83894

European-Finnish (FIN)

AF:

0.930

AC:

47113

AN:

50682

Middle Eastern (MID)

AF:

0.939

AC:

5400

AN:

5748

European-Non Finnish (NFE)

AF:

0.973

AC:

1072843

AN:

1102582

Other (OTH)

AF:

0.963

AC:

57411

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3515

7031

10546

14062

17577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21530

43060

64590

86120

107650

<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

AF:

0.970

AC:

147839

AN:

152354

Hom.:

71774

Cov.:

AF XY:

0.967

AC XY:

72063

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.988

AC:

41092

AN:

41584

American (AMR)

AF:

0.980

AC:

15003

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.977

AC:

3392

AN:

3472

East Asian (EAS)

AF:

0.908

AC:

4707

AN:

5184

South Asian (SAS)

AF:

0.914

AC:

4418

AN:

4832

European-Finnish (FIN)

AF:

0.923

AC:

9803

AN:

10618

Middle Eastern (MID)

AF:

0.946

AC:

278

AN:

294

European-Non Finnish (NFE)

AF:

0.973

AC:

66228

AN:

68032

Other (OTH)

AF:

0.966

AC:

2043

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

231

462

693

924

1155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.971

Hom.:

190405

Bravo

AF:

0.976

TwinsUK

AF:

0.974

AC:

3613

ALSPAC

AF:

0.972

AC:

3746

ESP6500AA

AF:

0.990

AC:

4332

ESP6500EA

AF:

0.971

AC:

8325

ExAC

AF:

0.957

AC:

114238

Asia WGS

AF:

0.900

AC:

3130

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.0

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.088

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

PhyloP100

0.36

PrimateAI

Benign

0.29

PROVEAN

Benign

4.1

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.028

ClinPred

0.0035

GERP RS

-0.84

Varity_R

0.23

gMVP

0.39

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over