Genetic Variant FUT3:p.Arg68Gly (chr19-5844638-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000303225.12(FUT3):c.202C>G(p.Arg68Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/20 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 0.0 ( 0 hom., cov: 21)

Failed GnomAD Quality Control

Consequence

FUT3
ENST00000303225.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04

Publications

79 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.202C>G	p.Arg68Gly	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.202C>G	p.Arg68Gly	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.202C>G	p.Arg68Gly	missense_variant	Exon 3 of 3	NP_001091109.3	P21217A8K737

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000589620.6 link	c.202C>G	p.Arg68Gly	missense_variant	Exon 3 of 3	1		ENSP00000465804.1		P21217

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148072

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71962

African (AFR)

AF:

0.00

AC:

AN:

40028

American (AMR)

AF:

0.00

AC:

AN:

14778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4876

South Asian (SAS)

AF:

0.00

AC:

AN:

4546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67048

Other (OTH)

AF:

0.00

AC:

AN:

2036

Alfa

AF:

0.00

Hom.:

137507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.010

.;.;.;.;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.50

.;.;.;.;T;T

M_CAP

Benign

0.0048

MetaRNN

Uncertain

0.47

T;T;T;T;T;T

MetaSVM

Benign

-0.94

PhyloP100

4.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.86

N;N;.;.;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0050

D;D;.;.;.;.

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Vest4

0.23

MutPred

0.65

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.17

MPC

0.71

ClinPred

0.43

GERP RS

2.3

gMVP

0.95

Mutation Taster

=94/6

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over