11-94544390-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002033.4(FUT4):​c.257C>G​(p.Ser86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Consequence

FUT4
NM_002033.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.244
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17923096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUT4NM_002033.4 linkc.257C>G p.Ser86Cys missense_variant Exon 1 of 1 ENST00000358752.4 NP_002024.1 P22083-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FUT4ENST00000358752.4 linkc.257C>G p.Ser86Cys missense_variant Exon 1 of 1 6 NM_002033.4 ENSP00000351602.2 P22083-1
PIWIL4ENST00000543336.5 linkn.-121+401C>G intron_variant Intron 1 of 13 2 ENSP00000444575.1 Q7Z3Z4-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.257C>G (p.S86C) 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 257, causing the serine (S) at amino acid position 86 to be replaced by a cysteine (C). 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
0.090
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
14
DANN
Benign
0.92
DEOGEN2
Benign
0.089
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.27
T
M_CAP
Uncertain
0.26
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.80
N
REVEL
Benign
0.063
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.093
T
Polyphen
0.98
D
Vest4
0.063
MutPred
0.20
Loss of phosphorylation at S86 (P = 0.0382);
MVP
0.47
MPC
0.89
ClinPred
0.18
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94277556; API