rs1553917304
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000203.5(IDUA):c.1115A>G(p.Asn372Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000203.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.1115A>G | p.Asn372Ser | missense_variant | Exon 8 of 14 | 2 | NM_000203.5 | ENSP00000425081.2 | ||
IDUA | ENST00000247933.9 | c.1115A>G | p.Asn372Ser | missense_variant | Exon 8 of 14 | 1 | ENSP00000247933.4 | |||
IDUA | ENST00000514698.5 | n.1222A>G | non_coding_transcript_exon_variant | Exon 5 of 11 | 5 | |||||
IDUA | ENST00000652070.1 | n.1171A>G | non_coding_transcript_exon_variant | Exon 7 of 13 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432042Hom.: 0 Cov.: 35 AF XY: 0.00000141 AC XY: 1AN XY: 710182
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 1 Pathogenic:1
This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 372 of the IDUA protein (p.Asn372Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 27146977). ClinVar contains an entry for this variant (Variation ID: 554765). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDUA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Hurler syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at