rs1553917737
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000203.5(IDUA):c.1845_1846del(p.Gly616LeufsTer42) variant causes a frameshift change. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
IDUA
NM_000203.5 frameshift
NM_000203.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.89
Genes affected
IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 24 pathogenic variants in the truncated region.
PP5
?
Variant 4-1004275-CTG-C is Pathogenic according to our data. Variant chr4-1004275-CTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 556253.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDUA | NM_000203.5 | c.1845_1846del | p.Gly616LeufsTer42 | frameshift_variant | 14/14 | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.1845_1846del | p.Gly616LeufsTer42 | frameshift_variant | 14/14 | 2 | NM_000203.5 | P1 | |
IDUA | ENST00000247933.9 | c.1845_1846del | p.Gly616LeufsTer42 | frameshift_variant | 14/14 | 1 | P1 | ||
IDUA | ENST00000514698.5 | n.1956_1957del | non_coding_transcript_exon_variant | 11/11 | 5 | ||||
IDUA | ENST00000652070.1 | n.1901_1902del | non_coding_transcript_exon_variant | 13/13 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hurler syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 23, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at