Variant chr19-5844014-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001382749.2(FUT3):c.826C>T(p.Pro276Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000874 in 1,613,544 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000089 ( 2 hom. )

Consequence

FUT3
NM_001382749.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT3	NM_001097639.3 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	3/3	ENST00000709635.1
FUT3	NM_001382749.2 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris
FUT3	ENST00000303225.12 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	3/3	1	P1
FUT3	ENST00000458379.7 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	2/2	1	P1
FUT3	ENST00000589620.6 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	3/3	1	P1
FUT3	ENST00000589918.5 linkuse as main transcript	c.826C>T	p.Pro276Ser	missense_variant	3/3	1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000137

AC:

AN:

240634

Hom.:

AF XY:

0.000167

AC XY:

AN XY:

131474

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000851

GnomAD4 exome

AF:

0.0000889

AC:

130

AN:

1461554

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000257

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.826C>T (p.P276S) alteration is located in exon 3 (coding exon 1) of the FUT3 gene. This alteration results from a C to T substitution at nucleotide position 826, causing the proline (P) at amino acid position 276 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-0.70

MutationTaster

Benign

0.72

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-7.1

D;D;.;.

REVEL

Benign

0.24

Sift

Uncertain

0.0060

D;D;.;.

Sift4G

Uncertain

0.016

D;D;D;D

Vest4

0.32

MutPred

0.76

Gain of catalytic residue at P276 (P = 0.0952);Gain of catalytic residue at P276 (P = 0.0952);Gain of catalytic residue at P276 (P = 0.0952);Gain of catalytic residue at P276 (P = 0.0952);

MVP

0.77

MPC

1.5

ClinPred

0.32

GERP RS

2.3

gMVP

0.68

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