Genetic Variant ENST00000303225.12:c.508G>A (chr19-5844332-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000303225.12(FUT3):c.508G>A(p.Gly170Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0465 in 1,613,770 control chromosomes in the GnomAD database, including 5,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1744 hom., cov: 31)

Exomes 𝑓: 0.040 ( 3919 hom. )

Consequence

FUT3
ENST00000303225.12 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.10

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018966794).

BP6

Variant 19-5844332-C-T is Benign according to our data. Variant chr19-5844332-C-T is described in ClinVar as [Benign]. Clinvar id is 242700.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.508G>A	p.Gly170Ser	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.508G>A	p.Gly170Ser	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.508G>A	p.Gly170Ser	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.508G>A	p.Gly170Ser	missense_variant	Exon 3 of 3	1		ENSP00000305603.5		P21217

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16707

AN:

151836

Hom.:

1728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0618

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0977

GnomAD3 exomes

AF:

0.0851

AC:

21246

AN:

249570

Hom.:

1989

AF XY:

0.0728

AC XY:

9845

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.0544

Gnomad FIN exome

AF:

0.0637

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0398

AC:

58216

AN:

1461816

Hom.:

3919

Cov.:

AF XY:

0.0382

AC XY:

27746

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.0527

Gnomad4 FIN exome

AF:

0.0613

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.110

AC:

16744

AN:

151954

Hom.:

1744

Cov.:

AF XY:

0.114

AC XY:

8438

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.0614

Gnomad4 FIN

AF:

0.0664

Gnomad4 NFE

AF:

0.0193

Gnomad4 OTH

AF:

0.0986

Alfa

AF:

0.0521

Hom.:

320

Bravo

AF:

0.127

ESP6500AA

AF:

0.247

AC:

1082

ESP6500EA

AF:

0.0172

AC:

147

ExAC

AF:

0.0815

AC:

9889

EpiCase

AF:

0.0148

EpiControl

AF:

0.0152

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

Uncertain

0.35

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.81

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.7

D;D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.011

D;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Vest4

0.12

MPC

1.4

ClinPred

0.027

GERP RS

2.2

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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