2-106145262-C-T

Variant summary

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

The NM_001253875.2(UXS1):​c.400G>A​(p.Val134Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,994 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UXS1
NM_001253875.2 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54
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.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UXS1NM_001253875.2 linkc.400G>A p.Val134Met missense_variant Exon 6 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.400G>A p.Val134Met missense_variant Exon 6 of 15 2 NM_001253875.2 ENSP00000283148.7 Q8NBZ7-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461684
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727120
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.385G>A (p.V129M) alteration is located in exon 6 (coding exon 6) of the UXS1 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the valine (V) at amino acid position 129 to be replaced by a methionine (M). 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
0.80
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.86
.;D;D
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Pathogenic
0.39
D
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Uncertain
2.5
.;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.017
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.79
MutPred
0.47
.;Gain of ubiquitination at K126 (P = 0.0754);.;
MVP
0.73
MPC
0.81
ClinPred
0.97
D
GERP RS
5.8
Varity_R
0.76
gMVP
0.85

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: rs762838871; hg19: chr2-106761718; COSMIC: COSV51680401; COSMIC: COSV51680401; API