NM_001371533.1:c.165A>G

Variant names:

• chr14-65561728-A-G
• rs2229677
• NM_001371533.1:c.165A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371533.1(FUT8):​c.165A>G​(p.Gln55Gln) 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:6
• Conservation: PhyloP100: 0.803
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation with defective fucosylation 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371533.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT8	NM_001371533.1	MANE Select	c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 11	NP_001358462.1	Q546E0
	FUT8	NM_001371536.1		c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 12	NP_001358465.1
	FUT8	NM_001371534.1		c.165A>G	p.Gln55Gln	synonymous	Exon 4 of 12	NP_001358463.1	Q546E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT8	ENST00000673929.1	MANE Select	c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 11	ENSP00000501213.1	Q9BYC5-1
	FUT8	ENST00000360689.9	TSL:1	c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 11	ENSP00000353910.5	Q9BYC5-1
	FUT8	ENST00000394586.6	TSL:1	c.165A>G	p.Gln55Gln	synonymous	Exon 2 of 10	ENSP00000378087.2	Q9BYC5-1

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

GnomAD2 exomes AF: 0.705 AC: 176424 AN: 250400 AF XY: 0.704

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 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

African (AFR) AF: 0.726 AC: 24277 AN: 33428

American (AMR) AF: 0.706 AC: 31510 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17938 AN: 26096

East Asian (EAS) AF: 0.902 AC: 35784 AN: 39670

South Asian (SAS) AF: 0.771 AC: 66510 AN: 86228

European-Finnish (FIN) AF: 0.620 AC: 33115 AN: 53402

Middle Eastern (MID) AF: 0.633 AC: 3644 AN: 5758

European-Non Finnish (NFE) AF: 0.682 AC: 758347 AN: 1111208

Other (OTH) AF: 0.705 AC: 42528 AN: 60340

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

African (AFR) AF: 0.731 AC: 30328 AN: 41478

American (AMR) AF: 0.701 AC: 10691 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4659 AN: 5178

South Asian (SAS) AF: 0.774 AC: 3725 AN: 4812

European-Finnish (FIN) AF: 0.608 AC: 6416 AN: 10544

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46034 AN: 67972

Other (OTH) AF: 0.675 AC: 1426 AN: 2112

Alfa AF: 0.685 Hom.: 58466

Bravo AF: 0.707

Asia WGS AF: 0.847 AC: 2943 AN: 3476

EpiCase AF: 0.668

EpiControl AF: 0.663

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital disorder of glycosylation with defective fucosylation 1 (1)
-	-	1	FUT8-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.5
DANN	Benign	0.56
PhyloP100		0.80
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229677; hg19: chr14-66028446; COSMIC: COSV108165620; COSMIC: COSV108165620;