2-106122984-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001253875.2(UXS1):​c.745G>T​(p.Ala249Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UXS1
NM_001253875.2 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77
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 Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity UXS1_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UXS1NM_001253875.2 linkc.745G>T p.Ala249Ser missense_variant Exon 9 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.745G>T p.Ala249Ser missense_variant Exon 9 of 15 2 NM_001253875.2 ENSP00000283148.7 Q8NBZ7-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461516
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727042
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
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
Feb 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.730G>T (p.A244S) alteration is located in exon 9 (coding exon 9) of the UXS1 gene. This alteration results from a G to T substitution at nucleotide position 730, causing the alanine (A) at amino acid position 244 to be replaced by a serine (S). 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
0.15
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.76
.;D;.;.;D;.;D
Eigen
Benign
0.091
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T;T;T;T;T;T;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.57
D
MutationAssessor
Benign
0.59
.;N;.;.;.;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-2.3
N;N;N;N;N;N;N
REVEL
Uncertain
0.58
Sift
Benign
0.19
T;T;T;T;T;T;T
Sift4G
Benign
0.15
T;T;T;.;.;T;.
Polyphen
0.66
P;P;.;.;.;.;.
Vest4
0.39
MutPred
0.68
.;Gain of catalytic residue at A244 (P = 0.0295);.;.;.;.;.;
MVP
0.45
MPC
1.6
ClinPred
0.86
D
GERP RS
4.9
Varity_R
0.56
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr2-106739440; API