Genetic Variant FUT4:p.Arg34Gly (chr11-94544233-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002033.4(FUT4):c.100C>G(p.Arg34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,323,958 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R34W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FUT4
NM_002033.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

3 publications found

Variant links:

Genes affected

FUT4 (HGNC:4015): (fucosyltransferase 4) The product of this gene transfers fucose to N-acetyllactosamine polysaccharides to generate fucosylated carbohydrate structures. It catalyzes the synthesis of the non-sialylated antigen, Lewis x (CD15). [provided by RefSeq, Jan 2009]

FUT4 links:

PIWIL4 (HGNC:18444): (piwi like RNA-mediated gene silencing 4) PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

PIWIL4 links:

ENSG00000304830 (HGNC:):

ENSG00000304830 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05492875).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002033.4. 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
	FUT4	NM_002033.4	MANE Select	c.100C>G	p.Arg34Gly	missense	Exon 1 of 1	NP_002024.1	P22083-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT4	ENST00000358752.4	TSL:6 MANE Select	c.100C>G	p.Arg34Gly	missense	Exon 1 of 1	ENSP00000351602.2	P22083-1
PIWIL4	ENST00000543336.5	TSL:2	n.-121+244C>G		intron	N/A	ENSP00000444575.1	Q7Z3Z4-3
ENSG00000304830	ENST00000806516.1		n.-89G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1323958

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

650726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26296

American (AMR)

AF:

0.00

AC:

AN:

24682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19406

East Asian (EAS)

AF:

0.00

AC:

AN:

31090

South Asian (SAS)

AF:

0.00

AC:

AN:

67352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3752

European-Non Finnish (NFE)

AF:

0.0000124

AC:

AN:

1051238

Other (OTH)

AF:

0.0000185

AC:

AN:

53938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.64

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.089

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.30

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.54

REVEL

Benign

0.031

Sift

Uncertain

0.029

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.057

MutPred

0.14

Gain of relative solvent accessibility (P = 0.0166)

MVP

0.20

MPC

1.0

ClinPred

0.11

GERP RS

-2.5

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.066

gMVP

0.090

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

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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