19-5831623-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_000150.4(FUT6):c.945C>A(p.Tyr315*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,613,814 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0085 ( 24 hom., cov: 31)

Exomes 𝑓: 0.010 ( 351 hom. )

Consequence

FUT6
NM_000150.4 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.74

Publications

15 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 -9 ACMG points.

BP6

Variant 19-5831623-G-T is Benign according to our data. Variant chr19-5831623-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 225367.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT6	NM_000150.4 link	c.945C>A	p.Tyr315*	stop_gained	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.945C>A	p.Tyr315*	stop_gained	Exon 3 of 3	2	NM_000150.4	ENSP00000313398.4		P51993-1

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1291

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00525

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.0174

AC:

4370

AN:

251054

AF XY:

0.0196

show subpopulations

Gnomad AFR exome

AF:

0.00291

Gnomad AMR exome

AF:

0.00541

Gnomad ASJ exome

AF:

0.0248

Gnomad EAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.00995

AC:

14546

AN:

1461500

Hom.:

351

Cov.:

AF XY:

0.0115

AC XY:

8355

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

33474

American (AMR)

AF:

0.00541

AC:

242

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

660

AN:

26128

East Asian (EAS)

AF:

0.0488

AC:

1936

AN:

39694

South Asian (SAS)

AF:

0.0561

AC:

4842

AN:

86240

European-Finnish (FIN)

AF:

0.00112

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00501

AC:

5576

AN:

1111962

Other (OTH)

AF:

0.0178

AC:

1073

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1250

2501

3751

5002

6252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.00846

AC:

1289

AN:

152314

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

673

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00308

AC:

128

AN:

41580

American (AMR)

AF:

0.00634

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.0620

AC:

321

AN:

5174

South Asian (SAS)

AF:

0.0531

AC:

256

AN:

4818

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00525

AC:

357

AN:

68028

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00992

Hom.:

Bravo

AF:

0.00829

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00675

AC:

ExAC

AF:

0.0176

AC:

2133

EpiCase

AF:

0.00758

EpiControl

AF:

0.00729

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fucosyltransferase 6 deficiency

Uncertain:1Benign:1

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

The heterozygous p.Tyr315Ter variant in FUT6 has been identified in at least 1 Indonesian individual with fucosyltransferase deficiency (PMID: 8175676). In vitro functional studies provide some evidence that the p.Tyr315Ter variant may impact protein function (PMID: 8175676). However, this variant was found in cis with another pathogenic variant and did not segregate with disease in multiple families, suggesting that it may not cause fucosyltransferase deficiency (PMID: 8175676). This variant is classified as benign for fucosyltransferase deficiency because it has been identified in >65% of East Asian chromosomes by ExAC (http://gnomad.broadinstitute.org/). -

Mar 18, 2016

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:reference population

- -

not provided

Benign:1

Jan 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.30

Eigen_PC

Benign

-0.0017

FATHMM_MKL

Uncertain

0.96

PhyloP100

2.7

Vest4

0.71

GERP RS

3.1

Mutation Taster

=113/87

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