Genetic Variant FUT6:p.Glu247Lys (chr19-5831829-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000150.4(FUT6):c.739G>A(p.Glu247Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,613,460 control chromosomes in the GnomAD database, including 5,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.12 ( 1889 hom., cov: 31)

Exomes 𝑓: 0.056 ( 3983 hom. )

Consequence

FUT6
NM_000150.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 2.27

Publications

32 publications found

Variant links:

Genes affected

FUT6 (HGNC:4017): (fucosyltransferase 6) The protein encoded by this gene is a Golgi stack membrane protein that is involved in the creation of sialyl-Lewis X, an E-selectin ligand. Mutations in this gene are a cause of fucosyltransferase-6 deficiency. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

FUT6 Gene-Disease associations (from GenCC):

fucosyltransferase 6 deficiency
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

FUT6 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=0.0040969253).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT6	NM_000150.4 link	c.739G>A	p.Glu247Lys	missense_variant	Exon 3 of 3	ENST00000318336.10	NP_000141.1	P51993-1Q6P7E6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT6	ENST00000318336.10 link	c.739G>A	p.Glu247Lys	missense_variant	Exon 3 of 3	2	NM_000150.4	ENSP00000313398.4		P51993-1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17761

AN:

151696

Hom.:

1884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0650

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0400

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.0775

AC:

19475

AN:

251182

AF XY:

0.0776

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.0419

Gnomad ASJ exome

AF:

0.0649

Gnomad EAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0428

Gnomad OTH exome

AF:

0.0643

GnomAD4 exome

AF:

0.0564

AC:

82396

AN:

1461646

Hom.:

3983

Cov.:

AF XY:

0.0584

AC XY:

42488

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.301

AC:

10065

AN:

33462

American (AMR)

AF:

0.0445

AC:

1989

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0677

AC:

1769

AN:

26132

East Asian (EAS)

AF:

0.0715

AC:

2837

AN:

39700

South Asian (SAS)

AF:

0.148

AC:

12723

AN:

86250

European-Finnish (FIN)

AF:

0.0294

AC:

1569

AN:

53408

Middle Eastern (MID)

AF:

0.0623

AC:

359

AN:

5762

European-Non Finnish (NFE)

AF:

0.0420

AC:

46659

AN:

1111842

Other (OTH)

AF:

0.0733

AC:

4426

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6271

12543

18814

25086

31357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2038

4076

6114

8152

10190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17806

AN:

151814

Hom.:

1889

Cov.:

AF XY:

0.116

AC XY:

8605

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.294

AC:

12117

AN:

41238

American (AMR)

AF:

0.0648

AC:

991

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3470

East Asian (EAS)

AF:

0.103

AC:

530

AN:

5150

South Asian (SAS)

AF:

0.137

AC:

655

AN:

4780

European-Finnish (FIN)

AF:

0.0290

AC:

307

AN:

10598

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0400

AC:

2720

AN:

67978

Other (OTH)

AF:

0.107

AC:

226

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

699

1398

2098

2797

3496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0609

Hom.:

563

Bravo

AF:

0.127

ESP6500AA

AF:

0.289

AC:

1273

ESP6500EA

AF:

0.0453

AC:

389

ExAC

AF:

0.0833

AC:

10117

Asia WGS

AF:

0.188

AC:

652

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Fucosyltransferase 6 deficiency

Uncertain:1Other:1

Mar 18, 2016

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:reference population

- -

Apr 29, 1994

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

0.070

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T;T;.

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

.;.;T;.;T

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.2

H;H;H;H;H

PhyloP100

2.3

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.9

D;D;D;D;.

REVEL

Uncertain

0.49

Sift

Uncertain

0.015

D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

0.92

P;P;P;P;.

Vest4

0.38

MPC

0.58

ClinPred

0.074

GERP RS

2.0

Varity_R

0.71

gMVP

0.78

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over