Variant 19-5831623-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 225367.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}. Variant chr19-5831623-G-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
FUT6	NM_000150.4 linkuse as main transcript	c.945C>A	p.Tyr315*	stop_gained	3/3	ENST00000318336.10	NP_000141.1	P51993-1Q6P7E6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT6	ENST00000318336.10 linkuse as main transcript	c.945C>A	p.Tyr315*	stop_gained	3/3	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

GnomAD3 exomes

AF:

0.0174

AC:

4370

AN:

251054

Hom.:

143

AF XY:

0.0196

AC XY:

2656

AN XY:

135784

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 SAS exome

AF:

0.0594

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

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00541

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0488

Gnomad4 SAS exome

AF:

0.0561

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00501

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.00846

AC:

1289

AN:

152314

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

673

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0620

Gnomad4 SAS

AF:

0.0531

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00525

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00757

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

Uncertain significance, criteria provided, single submitter	reference population	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	Mar 18, 2016	- -
Benign, criteria provided, single submitter	research	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	-	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/). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jan 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.30

Eigen_PC

Benign

-0.0017

FATHMM_MKL

Uncertain

0.96

Vest4

0.71

GERP RS

3.1

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