chr19-5843771-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000149.4(FUT3):c.1069G>A(p.Ala357Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FUT3
NM_000149.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.139

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12828118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.1069G>A	p.Ala357Thr	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.1069G>A	p.Ala357Thr	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.1069G>A	p.Ala357Thr	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.1069G>A	p.Ala357Thr	missense_variant	Exon 3 of 3	1	ENSP00000305603.5	P21217
FUT3	ENST00000458379.7 link	c.1069G>A	p.Ala357Thr	missense_variant	Exon 2 of 2	1	ENSP00000416443.1	P21217
FUT3	ENST00000589620.6 link	c.1069G>A	p.Ala357Thr	missense_variant	Exon 3 of 3	1	ENSP00000465804.1	P21217
FUT3	ENST00000589918.5 link	c.1069G>A	p.Ala357Thr	missense_variant	Exon 3 of 3	1	ENSP00000468123.1	P21217

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251376

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1069G>A (p.A357T) alteration is located in exon 3 (coding exon 1) of the FUT3 gene. This alteration results from a G to A substitution at nucleotide position 1069, causing the alanine (A) at amino acid position 357 to be replaced by a threonine (T). 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

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.5

DANN

Benign

0.93

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.11

M_CAP

Benign

0.010

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

N;N;.;.

REVEL

Benign

0.059

Sift

Benign

0.22

T;T;.;.

Sift4G

Benign

0.32

T;T;T;T

Vest4

0.12

MutPred

0.61

Gain of disorder (P = 0.1156);Gain of disorder (P = 0.1156);Gain of disorder (P = 0.1156);Gain of disorder (P = 0.1156);

MVP

0.22

MPC

0.57

ClinPred

0.28

GERP RS

2.2

gMVP

0.13

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