14-65561589-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001371533.1(FUT8):c.26G>A(p.Arg9His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

FUT8
NM_001371533.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

FUT8 (HGNC:4019): (fucosyltransferase 8) This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

FUT8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37991804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT8	NM_001371533.1 linkuse as main transcript	c.26G>A	p.Arg9His	missense_variant	3/11	ENST00000673929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT8	ENST00000673929.1 linkuse as main transcript	c.26G>A	p.Arg9His	missense_variant	3/11		NM_001371533.1	P1	Q9BYC5-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250930

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461208

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.26G>A (p.R9H) alteration is located in exon 3 (coding exon 1) of the FUT8 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the arginine (R) at amino acid position 9 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.21

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T;.;.;.;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.028

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.0

N;N;D;D;D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.011

D;D;.;D;.;D;D;D

Sift4G

Uncertain

0.040

D;D;D;D;.;D;D;D

Polyphen

1.0

D;D;.;.;.;.;.;.

Vest4

0.57

MutPred

0.37

Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);Gain of catalytic residue at W4 (P = 0.0024);

MVP

0.57

MPC

1.8

ClinPred

0.32

GERP RS

4.0

Varity_R

0.15

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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