rs187397780

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000149.4(FUT3):ā€‹c.1069G>Cā€‹(p.Ala357Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: š‘“ 0.000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000052 ( 0 hom. )

Consequence

FUT3
NM_000149.4 missense

Scores

2
14

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.21783325).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUT3NM_000149.4 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 NP_000140.1 P21217A8K737
FUT3NM_001097639.3 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 NP_001091108.3 P21217A8K737
FUT3NM_001097640.3 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 NP_001091109.3 P21217A8K737

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FUT3ENST00000303225.12 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 1 ENSP00000305603.5 P21217
FUT3ENST00000458379.7 linkc.1069G>C p.Ala357Pro missense_variant Exon 2 of 2 1 ENSP00000416443.1 P21217
FUT3ENST00000589620.6 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 1 ENSP00000465804.1 P21217
FUT3ENST00000589918.5 linkc.1069G>C p.Ala357Pro missense_variant Exon 3 of 3 1 ENSP00000468123.1 P21217

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251376
Hom.:
0
AF XY:
0.0000809
AC XY:
11
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:
0.000131
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000520
AC:
76
AN:
1461560
Hom.:
0
Cov.:
32
AF XY:
0.0000729
AC XY:
53
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:
0.000139
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152356
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000838
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
12
DANN
Uncertain
1.0
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.13
N
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.22
T;T;T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.4
N;N;.;.
REVEL
Benign
0.13
Sift
Benign
0.047
D;D;.;.
Sift4G
Benign
0.16
T;T;T;T
Vest4
0.39
MVP
0.35
MPC
1.6
ClinPred
0.89
D
GERP RS
2.2
gMVP
0.64

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.

Other links and lift over

dbSNP: rs187397780; hg19: chr19-5843782; API