Variant 19-5843773-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000149.4(FUT3):c.1067T>A(p.Ile356Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,613,650 control chromosomes in the GnomAD database, including 4,924 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.065 ( 381 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4543 hom. )

Consequence

FUT3
NM_000149.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016589463).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	NP_001091109.3	P21217A8K737

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
FUT3	ENST00000303225.12 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1	ENSP00000305603.5	P21217
FUT3	ENST00000458379.7 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 2 of 2	1	ENSP00000416443.1	P21217
FUT3	ENST00000589620.6 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1	ENSP00000465804.1	P21217
FUT3	ENST00000589918.5 link	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1	ENSP00000468123.1	P21217

Frequencies

GnomAD3 genomes

AF:

0.0652

AC:

9923

AN:

152184

Hom.:

378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0552

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0653

Gnomad OTH

AF:

0.0840

GnomAD3 exomes

AF:

0.0852

AC:

21414

AN:

251366

Hom.:

1242

AF XY:

0.0919

AC XY:

12485

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.0557

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.0884

GnomAD4 exome

AF:

0.0730

AC:

106716

AN:

1461346

Hom.:

4543

Cov.:

AF XY:

0.0766

AC XY:

55712

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0956

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.0570

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0848

GnomAD4 genome

AF:

0.0653

AC:

9945

AN:

152304

Hom.:

381

Cov.:

AF XY:

0.0671

AC XY:

5000

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.0654

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.0552

Gnomad4 NFE

AF:

0.0653

Gnomad4 OTH

AF:

0.0884

Alfa

AF:

0.0696

Hom.:

127

Bravo

AF:

0.0612

TwinsUK

AF:

0.0688

AC:

255

ALSPAC

AF:

0.0698

AC:

269

ESP6500AA

AF:

0.0336

AC:

148

ESP6500EA

AF:

0.0723

AC:

622

ExAC

AF:

0.0863

AC:

10479

Asia WGS

AF:

0.198

AC:

688

AN:

3478

EpiCase

AF:

0.0742

EpiControl

AF:

0.0724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.19

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.5

D;D;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.013

D;D;.;.

Sift4G

Uncertain

0.0020

D;D;D;D

Vest4

0.20

MPC

1.9

ClinPred

0.047

GERP RS

2.2

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over