Variant 14-65561603-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371533.1(FUT8):c.40A>G(p.Ile14Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FUT8
NM_001371533.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

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:

FUT8 (HGNC:):

FUT8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121059954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT8	NM_001371533.1 linkuse as main transcript	c.40A>G	p.Ile14Val	missense_variant	3/11	ENST00000673929.1	NP_001358462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT8	ENST00000673929.1 linkuse as main transcript	c.40A>G	p.Ile14Val	missense_variant	3/11		NM_001371533.1	ENSP00000501213.1		Q9BYC5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461298

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

May 28, 2024

The c.40A>G (p.I14V) alteration is located in exon 3 (coding exon 1) of the FUT8 gene. This alteration results from a A to G substitution at nucleotide position 40, causing the isoleucine (I) at amino acid position 14 to be replaced by a valine (V). 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

Benign

0.15

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.19

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

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

.;T;D;T;.;T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.12

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

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

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.39

N;N;N;N;N;N;N;N

REVEL

Benign

0.091

Sift

Benign

0.58

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

Sift4G

Benign

1.0

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

Polyphen

0.0

B;B;.;.;.;.;.;.

Vest4

0.13

MVP

0.34

MPC

0.50

ClinPred

0.80

GERP RS

4.5

Varity_R

0.059

gMVP

0.55

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