10-133357993-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001301828.2(FUOM):​c.-328G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000596 in 1,509,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

FUOM
NM_001301828.2 5_prime_UTR_premature_start_codon_gain

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120
Variant links:
Genes affected
FUOM (HGNC:24733): (fucose mutarotase) Predicted to enable L-fucose mutarotase activity and fucose binding activity. Predicted to be involved in fucose metabolic process and fucosylation. Predicted to act upstream of or within female mating behavior and negative regulation of neuron differentiation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUOMNM_001098483.3 linkc.15G>T p.Lys5Asn missense_variant Exon 1 of 6 ENST00000278025.9 NP_001091953.1 A2VDF0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FUOMENST00000278025.9 linkc.15G>T p.Lys5Asn missense_variant Exon 1 of 6 1 NM_001098483.3 ENSP00000278025.5 A2VDF0-1
FUOMENST00000368552.7 linkc.15G>T p.Lys5Asn missense_variant Exon 1 of 6 1 ENSP00000357540.5 A2VDF0-2
FUOMENST00000447176.5 linkc.3G>T p.Lys1Asn missense_variant Exon 1 of 5 2 ENSP00000413379.2 X6RK00
FUOMENST00000465384.5 linkn.9G>T non_coding_transcript_exon_variant Exon 1 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000655
AC:
7
AN:
106936
Hom.:
0
AF XY:
0.0000168
AC XY:
1
AN XY:
59662
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000322
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000516
AC:
7
AN:
1357456
Hom.:
0
Cov.:
32
AF XY:
0.00000299
AC XY:
2
AN XY:
669460
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000212
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000505
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.15G>T (p.K5N) alteration is located in exon 1 (coding exon 1) of the FUOM gene. This alteration results from a G to T substitution at nucleotide position 15, causing the lysine (K) at amino acid position 5 to be replaced by an asparagine (N). 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
Pathogenic
0.69
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T;.;T
Eigen
Benign
0.044
Eigen_PC
Benign
-0.10
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.74
T;T;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.74
D;D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Pathogenic
3.1
M;M;.
PrimateAI
Pathogenic
0.94
D
PROVEAN
Uncertain
-3.4
D;D;.
REVEL
Uncertain
0.48
Sift
Benign
0.043
D;T;.
Sift4G
Uncertain
0.051
T;D;D
Polyphen
0.93
P;D;.
Vest4
0.32
MutPred
0.81
Loss of ubiquitination at K5 (P = 0.0155);Loss of ubiquitination at K5 (P = 0.0155);.;
MVP
0.22
MPC
0.099
ClinPred
0.92
D
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.43
gMVP
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs749267993; hg19: chr10-135171497; API