rs17279736

Variant names:

• chr2-106140909-G-C
• rs17279736
• NM_001253875.2:c.472+4281C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001253875.2(UXS1):​c.472+4281C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 5,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5084 hom., cov: 32)
• Consequence: UXS1 NM_001253875.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UXS1	NM_001253875.2	MANE Select	c.472+4281C>G		intron	N/A	NP_001240804.1
	UXS1	NM_025076.5		c.457+4281C>G		intron	N/A	NP_079352.2
	UXS1	NM_001377504.1		c.472+4281C>G		intron	N/A	NP_001364433.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UXS1	ENST00000283148.12	TSL:2 MANE Select	c.472+4281C>G		intron	N/A	ENSP00000283148.7
	UXS1	ENST00000409501.7	TSL:1	c.457+4281C>G		intron	N/A	ENSP00000387019.3
	UXS1	ENST00000457835.5	TSL:4	c.286+4281C>G		intron	N/A	ENSP00000399316.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37671 AN: 151954 Hom.: 5081 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37703 AN: 152074 Hom.: 5084 Cov.: 32 AF XY: 0.242 AC XY: 17957 AN XY: 74354

African (AFR) AF: 0.192 AC: 7968 AN: 41482

American (AMR) AF: 0.203 AC: 3106 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 350 AN: 5186

South Asian (SAS) AF: 0.206 AC: 994 AN: 4826

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10546

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20855 AN: 67974

Other (OTH) AF: 0.241 AC: 507 AN: 2104

Alfa AF: 0.272 Hom.: 706

Bravo AF: 0.243

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.43
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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: rs17279736; hg19: chr2-106757365; COSMIC: COSV51676135; COSMIC: COSV51676135;