chr2-106125655-C-A

Variant names:

• chr2-106125655-C-A
• NM_001253875.2:c.602G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

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. R201C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: UXS1 NM_001253875.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UXS1	NM_001253875.2	c.602G>T	p.Arg201Leu	missense_variant	Exon 8 of 15	ENST00000283148.12	NP_001240804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UXS1	ENST00000283148.12	c.602G>T	p.Arg201Leu	missense_variant	Exon 8 of 15	2	NM_001253875.2	ENSP00000283148.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000420 AC: 6 AN: 1427254 Hom.: 0 Cov.: 29 AF XY: 0.00000566 AC XY: 4 AN XY: 706448

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000457

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	.;D;.;.;D;.;D;.
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.1	.;M;.;.;.;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.;.;D;.;.
Polyphen		1.0	D;D;.;.;.;.;.;.
Vest4		0.89
MutPred		0.75		.;Loss of MoRF binding (P = 0.0039);.;.;.;.;.;.;
MVP		0.94
MPC		1.7
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-106742111;