Genetic Variant NM_001253875.2:c.602G>T (chr2-106125655-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_001253875.2(UXS1):c.602G>T(p.Arg201Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,427,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

UXS1
NM_001253875.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43

Publications

0 publications found

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]

UXS1 Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

UXS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253875.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UXS1	NM_001253875.2	MANE Select	c.602G>T	p.Arg201Leu	missense	Exon 8 of 15	NP_001240804.1	Q8NBZ7-2
UXS1	NM_025076.5		c.587G>T	p.Arg196Leu	missense	Exon 8 of 15	NP_079352.2
UXS1	NM_001377504.1		c.602G>T	p.Arg201Leu	missense	Exon 8 of 13	NP_001364433.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UXS1	ENST00000283148.12	TSL:2 MANE Select	c.602G>T	p.Arg201Leu	missense	Exon 8 of 15	ENSP00000283148.7	Q8NBZ7-2
UXS1	ENST00000409501.7	TSL:1	c.587G>T	p.Arg196Leu	missense	Exon 8 of 15	ENSP00000387019.3	Q8NBZ7-1
UXS1	ENST00000409032.5	TSL:1	c.83G>T	p.Arg28Leu	missense	Exon 3 of 10	ENSP00000387096.1	Q8NBZ7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000420

AC:

AN:

1427254

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32670

American (AMR)

AF:

0.00

AC:

AN:

39886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25476

East Asian (EAS)

AF:

0.00

AC:

AN:

37872

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000457

AC:

AN:

1094372

Other (OTH)

AF:

0.00

AC:

AN:

59188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.53

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.95

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.1

PhyloP100

7.4

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.7

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.89

MutPred

0.75

Loss of MoRF binding (P = 0.0039)

MVP

0.94

MPC

1.7

ClinPred

1.0

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.94

Mutation Taster

=27/73

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over