rs1297536872

Variant names:

• chr14-65721948-C-G
• rs1297536872
• NM_001371533.1:c.1009C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-65721948-C-G
• chr14-65721948-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001371533.1(FUT8):​c.1009C>G​(p.Arg337Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R337C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT8 NM_001371533.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91
• Publications: 3 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908
• PP5: Variant 14-65721948-C-G is Pathogenic according to our data. Variant chr14-65721948-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 545466.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1009C>G	p.Arg337Gly	missense	Exon 8 of 11	NP_001358462.1	Q546E0
	FUT8	NM_001371536.1		c.1111C>G	p.Arg371Gly	missense	Exon 9 of 12	NP_001358465.1
	FUT8	NM_001371534.1		c.1009C>G	p.Arg337Gly	missense	Exon 9 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.1009C>G	p.Arg337Gly	missense	Exon 8 of 11	ENSP00000501213.1	Q9BYC5-1
	FUT8	ENST00000360689.9	TSL:1	c.1009C>G	p.Arg337Gly	missense	Exon 8 of 11	ENSP00000353910.5	Q9BYC5-1
	FUT8	ENST00000394586.6	TSL:1	c.1009C>G	p.Arg337Gly	missense	Exon 7 of 10	ENSP00000378087.2	Q9BYC5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital disorder of glycosylation with defective fucosylation 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.91	D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.96
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.64		Gain of catalytic residue at P338 (P = 2e-04)
MVP		0.98
MPC		1.8
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.90
gMVP		0.95
Mutation Taster		=0/100	disease causing (ClinVar)

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: rs1297536872; hg19: chr14-66188666;