10-133356698-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001098483.3(FUOM):​c.266G>T​(p.Gly89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FUOM
NM_001098483.3 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38471523).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUOMNM_001098483.3 linkc.266G>T p.Gly89Val missense_variant Exon 4 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.266G>T p.Gly89Val missense_variant Exon 4 of 6 1 NM_001098483.3 ENSP00000278025.5 A2VDF0-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447828
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
718172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.06e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.266G>T (p.G89V) alteration is located in exon 4 (coding exon 4) of the FUOM gene. This alteration results from a G to T substitution at nucleotide position 266, causing the glycine (G) at amino acid position 89 to be replaced by a valine (V). 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
0.32
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.070
T;.;T;.
Eigen
Benign
-0.054
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.23
N
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Pathogenic
3.0
M;M;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-6.3
D;D;D;D
REVEL
Uncertain
0.56
Sift
Benign
0.058
T;D;T;D
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.90
P;D;.;.
Vest4
0.47
MutPred
0.55
Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);.;.;
MVP
0.22
MPC
0.21
ClinPred
0.98
D
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.56

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: chr10-135170202; API