rs17279736

chr2-106140909-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UXS1	NM_001253875.2	c.472+4281C>G		intron_variant		ENST00000283148.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UXS1	ENST00000283148.12	c.472+4281C>G		intron_variant		2	NM_001253875.2	A1

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

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.241

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
Dann	Benign	0.43

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

Other links and lift over

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