rs1226056948
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000203.5(IDUA):c.300-3C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000203.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDUA | NM_000203.5 | c.300-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.300-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_000203.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250066Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135684
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458674Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725786
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-I-H/S Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2000 | - - |
Mucopolysaccharidosis type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2023 | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 551563). This variant has been observed in individual(s) with mucopolysaccharidosis (PMID: 10735634, 29801497). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change falls in intron 2 of the IDUA gene. It does not directly change the encoded amino acid sequence of the IDUA protein. It affects a nucleotide within the consensus splice site. - |
Hurler syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Apr 18, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at