2-106104831-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001253875.2(UXS1):​c.886G>A​(p.Gly296Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UXS1
NM_001253875.2 missense

Scores

15
3
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92
Variant links:
Genes affected
UXS1 (HGNC:17729): (UDP-glucuronate decarboxylase 1) This gene encodes an enzyme found in the perinuclear Golgi which catalyzes the synthesis of UDP-xylose used in glycosaminoglycan (GAG) synthesis on proteoglycans. The GAG chains are covalently attached to proteoglycans which participate in signaling pathways during development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UXS1NM_001253875.2 linkc.886G>A p.Gly296Arg missense_variant Exon 11 of 15 ENST00000283148.12 NP_001240804.1 Q8NBZ7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UXS1ENST00000283148.12 linkc.886G>A p.Gly296Arg missense_variant Exon 11 of 15 2 NM_001253875.2 ENSP00000283148.7 Q8NBZ7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461706
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727132
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.871G>A (p.G291R) alteration is located in exon 11 (coding exon 11) of the UXS1 gene. This alteration results from a G to A substitution at nucleotide position 871, causing the glycine (G) at amino acid position 291 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.53
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.89
.;D;.;.;D
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.92
D;D;D;D;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.5
.;H;.;.;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-7.6
D;D;D;D;D
REVEL
Pathogenic
0.94
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;.;.
Polyphen
1.0
D;D;.;.;.
Vest4
0.97
MutPred
0.94
.;Loss of glycosylation at S292 (P = 0.0584);.;.;.;
MVP
0.88
MPC
1.5
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.67
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1677918716; hg19: chr2-106721287; COSMIC: COSV104620808; COSMIC: COSV104620808; API