14-65561728-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371533.1(FUT8):c.165A>G(p.Gln55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,612,804 control chromosomes in the GnomAD database, including 391,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37609 hom., cov: 33)
  • Exomes 𝑓: 0.69 (353448 hom.)
• Consequence: FUT8 NM_001371533.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.803

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 14-65561728-A-G is Benign according to our data. Variant chr14-65561728-A-G is described in ClinVar as [Benign]. Clinvar id is 402887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.803 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT8	NM_001371533.1	c.165A>G	p.Gln55=	synonymous_variant	3/11	ENST00000673929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT8	ENST00000673929.1	c.165A>G	p.Gln55=	synonymous_variant	3/11		NM_001371533.1	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106415 AN: 151896 Hom.: 37565 Cov.: 33

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.672

GnomAD3 exomes AF: 0.705 AC: 176424 AN: 250400 Hom.: 62843 AF XY: 0.704 AC XY: 95205 AN XY: 135298

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.691

Gnomad EAS exome AF: 0.902

Gnomad SAS exome AF: 0.769

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.694 AC: 1013653 AN: 1460790 Hom.: 353448 Cov.: 48 AF XY: 0.695 AC XY: 505249 AN XY: 726710

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.701 AC: 106516 AN: 152014 Hom.: 37609 Cov.: 33 AF XY: 0.702 AC XY: 52161 AN XY: 74302

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.675

Alfa AF: 0.680 Hom.: 39677

Bravo AF: 0.707

Asia WGS AF: 0.847 AC: 2943 AN: 3476

EpiCase AF: 0.668

EpiControl AF: 0.663

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Congenital disorder of glycosylation with defective fucosylation 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

FUT8-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	7.5
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs2229677; hg19: chr14-66028446;