dbSNP rs150418165: FUT3:p.Arg323Pro (chr19-5843872-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000149.4(FUT3):c.968G>C(p.Arg323Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,612,820 control chromosomes in the GnomAD database, including 1 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R323Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FUT3
NM_000149.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01872778).

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.968G>C	p.Arg323Pro	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.968G>C	p.Arg323Pro	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.968G>C	p.Arg323Pro	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.968G>C	p.Arg323Pro	missense_variant	Exon 3 of 3	1	ENSP00000305603.5	P21217
FUT3	ENST00000458379.7 link	c.968G>C	p.Arg323Pro	missense_variant	Exon 2 of 2	1	ENSP00000416443.1	P21217
FUT3	ENST00000589620.6 link	c.968G>C	p.Arg323Pro	missense_variant	Exon 3 of 3	1	ENSP00000465804.1	P21217
FUT3	ENST00000589918.5 link	c.968G>C	p.Arg323Pro	missense_variant	Exon 3 of 3	1	ENSP00000468123.1	P21217

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

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:

0.00430

GnomAD3 exomes

AF:

0.000542

AC:

136

AN:

251132

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00729

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000223

AC:

325

AN:

1460502

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

137

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.00790

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152318

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00750

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.00257

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000766

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.23

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.60

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Uncertain

-0.28

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.6

D;D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D

Vest4

0.59

MVP

0.69

MPC

1.8

ClinPred

0.15

GERP RS

2.3

gMVP

0.97

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