ENST00000303225.12:c.59T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The ENST00000303225.12(FUT3):c.59T>G(p.Leu20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,776 control chromosomes in the GnomAD database, including 17,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 3212 hom., cov: 33)

Exomes 𝑓: 0.12 ( 14130 hom. )

Consequence

FUT3
ENST00000303225.12 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.529

Variant links:

Genes affected

FUT3 (HGNC:4014): (fucosyltransferase 3 (Lewis blood group)) The Lewis histo-blood group system comprises a set of fucosylated glycosphingolipids that are synthesized by exocrine epithelial cells and circulate in body fluids. The glycosphingolipids function in embryogenesis, tissue differentiation, tumor metastasis, inflammation, and bacterial adhesion. They are secondarily absorbed to red blood cells giving rise to their Lewis phenotype. This gene is a member of the fucosyltransferase family, which catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. It encodes an enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Mutations in this gene are responsible for the majority of Lewis antigen-negative phenotypes. Differences in the expression of this gene are associated with host susceptibility to viral infection. [provided by RefSeq, Aug 2020]

FUT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07336402).

BP6

Variant 19-5844781-A-C is Benign according to our data. Variant chr19-5844781-A-C is described in ClinVar as [Benign]. Clinvar id is 242770.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.59T>G	p.Leu20Arg	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.59T>G	p.Leu20Arg	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.59T>G	p.Leu20Arg	missense_variant	Exon 3 of 3	NP_001091109.3	P21217A8K737

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000303225.12 link	c.59T>G	p.Leu20Arg	missense_variant	Exon 3 of 3	1		ENSP00000305603.5		P21217

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27548

AN:

152030

Hom.:

3194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0939

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.176

AC:

44047

AN:

250298

Hom.:

4891

AF XY:

0.170

AC XY:

23060

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.0980

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.122

AC:

177670

AN:

1461628

Hom.:

14130

Cov.:

AF XY:

0.123

AC XY:

89702

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.0923

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.181

AC:

27602

AN:

152148

Hom.:

3212

Cov.:

AF XY:

0.187

AC XY:

13927

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.0939

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.0969

Hom.:

512

Bravo

AF:

0.193

TwinsUK

AF:

0.0982

AC:

364

ALSPAC

AF:

0.0981

AC:

378

ESP6500AA

AF:

0.282

AC:

1244

ESP6500EA

AF:

0.0984

AC:

846

ExAC

AF:

0.173

AC:

21065

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

EpiCase

AF:

0.0978

EpiControl

AF:

0.0963

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FUT3-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

.;.;.;.;.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

.;.;.;.;T;T;T

MetaRNN

Benign

0.073

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.6

D;D;.;.;.;.;.

REVEL

Benign

0.27

Sift

Benign

0.035

D;D;.;.;.;.;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;.

Vest4

0.18

MPC

1.8

ClinPred

0.030

GERP RS

2.3

gMVP

0.87

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