Genetic Variant FUT4:p.Pro83Arg (chr11-94544381-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002033.4(FUT4):c.248C>G(p.Pro83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,389,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FUT4
NM_002033.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09563735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4 link	c.248C>G	p.Pro83Arg	missense_variant	Exon 1 of 1	ENST00000358752.4	NP_002024.1	P22083-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FUT4	ENST00000358752.4 link	c.248C>G	p.Pro83Arg	missense_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2	P22083-1
PIWIL4	ENST00000543336.5 link	n.-121+392C>G		intron_variant	Intron 1 of 13	2		ENSP00000444575.1	Q7Z3Z4-3
ENSG00000304830	ENST00000806516.1 link	n.-237G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000360

AC:

AN:

1389402

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29598

American (AMR)

AF:

0.00

AC:

AN:

38712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24844

East Asian (EAS)

AF:

0.00

AC:

AN:

34892

South Asian (SAS)

AF:

0.00

AC:

AN:

80112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4360

European-Non Finnish (NFE)

AF:

0.00000461

AC:

AN:

1084086

Other (OTH)

AF:

0.00

AC:

AN:

57836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 31, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.248C>G (p.P83R) alteration is located in exon 1 (coding exon 1) of the FUT4 gene. This alteration results from a C to G substitution at nucleotide position 248, causing the proline (P) at amino acid position 83 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.29

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

REVEL

Benign

0.020

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

0.011

Vest4

0.067

MutPred

0.30

Gain of MoRF binding (P = 0.0016);

MVP

0.28

MPC

0.97

ClinPred

0.31

GERP RS

0.94

PromoterAI

0.27

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.095

Mutation Taster

=88/12

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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chr11-94544381-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over