dbSNP rs778986: FUT3:p.Met105Thr (chr19-5844526-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000303225.12(FUT3):c.314T>C(p.Met105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,614,000 control chromosomes in the GnomAD database, including 559,004 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.84 ( 54247 hom., cov: 32)

Exomes 𝑓: 0.83 ( 504757 hom. )

Consequence

FUT3
ENST00000303225.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

73 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.6690175E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FUT3	NM_000149.4 link	c.314T>C	p.Met105Thr	missense_variant	Exon 3 of 3	NP_000140.1	P21217A8K737
FUT3	NM_001097639.3 link	c.314T>C	p.Met105Thr	missense_variant	Exon 3 of 3	NP_001091108.3	P21217A8K737
FUT3	NM_001097640.3 link	c.314T>C	p.Met105Thr	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.314T>C	p.Met105Thr	missense_variant	Exon 3 of 3	1		ENSP00000465804.1		P21217

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128130

AN:

152004

Hom.:

54177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.801

Gnomad MID

AF:

0.793

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.800

GnomAD2 exomes

AF:

0.840

AC:

211131

AN:

251484

AF XY:

0.834

show subpopulations

Gnomad AFR exome

AF:

0.888

Gnomad AMR exome

AF:

0.903

Gnomad ASJ exome

AF:

0.783

Gnomad EAS exome

AF:

0.972

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.807

Gnomad OTH exome

AF:

0.818

GnomAD4 exome

AF:

0.830

AC:

1213034

AN:

1461876

Hom.:

504757

Cov.:

AF XY:

0.828

AC XY:

602151

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.890

AC:

29801

AN:

33480

American (AMR)

AF:

0.898

AC:

40168

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

20368

AN:

26136

East Asian (EAS)

AF:

0.982

AC:

38998

AN:

39700

South Asian (SAS)

AF:

0.829

AC:

71493

AN:

86258

European-Finnish (FIN)

AF:

0.801

AC:

42812

AN:

53418

Middle Eastern (MID)

AF:

0.780

AC:

4497

AN:

5768

European-Non Finnish (NFE)

AF:

0.822

AC:

914506

AN:

1111996

Other (OTH)

AF:

0.834

AC:

50391

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15108

30217

45325

60434

75542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.843

AC:

128260

AN:

152124

Hom.:

54247

Cov.:

AF XY:

0.841

AC XY:

62549

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.888

AC:

36871

AN:

41510

American (AMR)

AF:

0.859

AC:

13134

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2694

AN:

3470

East Asian (EAS)

AF:

0.972

AC:

5011

AN:

5156

South Asian (SAS)

AF:

0.842

AC:

4058

AN:

4822

European-Finnish (FIN)

AF:

0.801

AC:

8479

AN:

10586

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.812

AC:

55220

AN:

67974

Other (OTH)

AF:

0.804

AC:

1698

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1051

2101

3152

4202

5253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.825

Hom.:

157496

Bravo

AF:

0.853

TwinsUK

AF:

0.830

AC:

3078

ALSPAC

AF:

0.830

AC:

3199

ESP6500AA

AF:

0.892

AC:

3929

ESP6500EA

AF:

0.812

AC:

6981

ExAC

AF:

0.837

AC:

101601

Asia WGS

AF:

0.926

AC:

3220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.0

(source)

DANN

Benign

0.53

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.21

.;.;.;.;T

MetaRNN

Benign

0.0000047

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.32

PrimateAI

Benign

0.37

PROVEAN

Benign

0.90

N;N;.;.;.

REVEL

Benign

0.032

Sift

Benign

0.038

D;D;.;.;.

Sift4G

Uncertain

0.024

D;D;D;D;T

Vest4

0.075

MPC

0.64

ClinPred

0.0042

GERP RS

-0.40

gMVP

0.65

Mutation Taster

=100/0

polymorphism (auto)

(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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rs778986

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over