Genetic Variant FUT9:p.Arg328Gln (chr6-96204138-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_006581.4(FUT9):c.983G>A(p.Arg328Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000149 in 1,343,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000015 ( 0 hom. )

Consequence

FUT9
NM_006581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Publications

6 publications found

Variant links:

Genes affected

FUT9 (HGNC:4020): (fucosyltransferase 9) The protein encoded by this gene belongs to the glycosyltransferase family. It is localized to the golgi, and catalyzes the last step in the biosynthesis of Lewis X (LeX) antigen, the addition of a fucose to precursor polysaccharides. This protein is one of the few fucosyltransferases that synthesizes the LeX oligosaccharide (CD15) expressed in the organ buds progressing in mesenchyma during embryogenesis. It is also responsible for the expression of CD15 in mature granulocytes. A common haplotype of this gene has also been associated with susceptibility to placental malaria infection. [provided by RefSeq, Nov 2011]

FUT9 links:

UFL1-AS1 (HGNC:41007): (UFL1 antisense RNA 1)

UFL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a mutagenesis_site Decreases catalytic efficiency toward type 2 LacNAc, LNnT and H-type 2 LacNAc by 3320-fold, 1280-fold and 3060-fold, respectively; when associated with F-327 and F-329 del. (size 0) in uniprot entity FUT9_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09519267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006581.4. 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
	FUT9	NM_006581.4	MANE Select	c.983G>A	p.Arg328Gln	missense	Exon 3 of 3	NP_006572.2	Q9Y231

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT9	ENST00000302103.6	TSL:1 MANE Select	c.983G>A	p.Arg328Gln	missense	Exon 3 of 3	ENSP00000302599.4	Q9Y231
FUT9	ENST00000887181.1		c.983G>A	p.Arg328Gln	missense	Exon 4 of 4	ENSP00000557240.1
FUT9	ENST00000887182.1		c.983G>A	p.Arg328Gln	missense	Exon 4 of 4	ENSP00000557241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1343016

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

655088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29976

American (AMR)

AF:

0.00

AC:

AN:

27956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19496

East Asian (EAS)

AF:

0.00

AC:

AN:

38624

South Asian (SAS)

AF:

0.00

AC:

AN:

63704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1053536

Other (OTH)

AF:

0.00

AC:

AN:

55298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.033

Eigen

Benign

-0.25

Eigen_PC

Benign

0.0046

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0038

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.025

PhyloP100

3.7

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.65

REVEL

Benign

0.096

Sift

Benign

0.58

Sift4G

Benign

0.61

Polyphen

0.0040

Vest4

0.18

MutPred

0.59

Loss of MoRF binding (P = 0.0686)

MVP

0.39

MPC

0.80

ClinPred

0.36

GERP RS

5.5

Varity_R

0.091

gMVP

0.53

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over