NM_001253875.2:c.184G>C

Variant names:

• chr2-106164738-C-G
• NM_001253875.2:c.184G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001253875.2(UXS1):​c.184G>C​(p.Glu62Gln) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UXS1 NM_001253875.2 missense, splice_region
• Scores: Splicing: ADA: 0.7704
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.27
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18310729).

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.184G>C	p.Glu62Gln	missense splice_region	Exon 3 of 15	NP_001240804.1	Q8NBZ7-2
	UXS1	NM_025076.5		c.169G>C	p.Glu57Gln	missense splice_region	Exon 3 of 15	NP_079352.2
	UXS1	NM_001377504.1		c.184G>C	p.Glu62Gln	missense splice_region	Exon 3 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.184G>C	p.Glu62Gln	missense splice_region	Exon 3 of 15	ENSP00000283148.7	Q8NBZ7-2
	UXS1	ENST00000409501.7	TSL:1	c.169G>C	p.Glu57Gln	missense splice_region	Exon 3 of 15	ENSP00000387019.3	Q8NBZ7-1
	UXS1	ENST00000903971.1		c.169G>C	p.Glu57Gln	missense splice_region	Exon 3 of 16	ENSP00000574030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	Benign	0.094
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.027
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	0.55	N
PhyloP100		5.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.31
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.037	B
Vest4		0.36
MutPred		0.26		Loss of helix (P = 0.0237)
MVP		0.65
MPC		0.83
ClinPred		0.60	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.56
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.77
dbscSNV1_RF	Benign	0.60
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

Other links and lift over

hg19: chr2-106781194;