chr2-106145232-C-T

Variant names:

• chr2-106145232-C-T
• rs1389354033
• NM_001253875.2:c.430G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001253875.2(UXS1):​c.430G>A​(p.Glu144Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UXS1 NM_001253875.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 2 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UXS1	NM_001253875.2	MANE Select	c.430G>A	p.Glu144Lys	missense	Exon 6 of 15	NP_001240804.1	Q8NBZ7-2
	UXS1	NM_025076.5		c.415G>A	p.Glu139Lys	missense	Exon 6 of 15	NP_079352.2
	UXS1	NM_001377504.1		c.430G>A	p.Glu144Lys	missense	Exon 6 of 13	NP_001364433.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UXS1	ENST00000283148.12	TSL:2 MANE Select	c.430G>A	p.Glu144Lys	missense	Exon 6 of 15	ENSP00000283148.7	Q8NBZ7-2
	UXS1	ENST00000409501.7	TSL:1	c.415G>A	p.Glu139Lys	missense	Exon 6 of 15	ENSP00000387019.3	Q8NBZ7-1
	UXS1	ENST00000903971.1		c.415G>A	p.Glu139Lys	missense	Exon 6 of 16	ENSP00000574030.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.84	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Benign	0.93	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.61		Gain of methylation at E139 (P = 0.0134)
MVP		0.75
MPC		1.7
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.86
gMVP		0.93
Mutation Taster		=9/91	disease causing

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

Other links and lift over

dbSNP: rs1389354033; hg19: chr2-106761688;