Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000203.5(IDUA):c.439C>T (p.Gln147Ter)

CA355961461

984179 (ClinVar)

Gene: IDUA (HGNC:3425)

Condition: mucopolysaccharidosis type 1 (MONDO:0001586)

Inheritance Mode: Autosomal recessive inheritance

UUID: a1bbb46f-f9f8-4458-92f1-c03a31c770bc

Approved on: 2024-12-05

Published on: 2025-03-19

HGVS expressions

NM_000203.5(IDUA):c.439C>T (p.Gln147Ter)

NM_000203.5:c.439C>T

NC_000004.12:g.1000935C>T

CM000666.2:g.1000935C>T

NC_000004.11:g.994723C>T

CM000666.1:g.994723C>T

NC_000004.10:g.984723C>T

NG_008103.1:g.18939C>T

ENST00000247933.9:c.439C>T

ENST00000514224.2:c.439C>T

ENST00000652070.1:n.495C>T

ENST00000247933.8:c.439C>T

ENST00000502910.5:c.298C>T

ENST00000504568.5:c.399C>T

ENST00000506561.5:n.448C>T

ENST00000508168.5:n.317C>T

ENST00000509948.5:c.232C>T

ENST00000514192.5:c.256C>T

ENST00000514224.1:c.43C>T

ENST00000514698.5:n.339C>T

NM_000203.4:c.439C>T

NR_110313.1:n.527C>T

NM_001363576.1:c.43C>T

Likely Pathogenic

PVS1 PM2_Supporting

PM3 PP4

Evidence Links 0

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specification: ClinGen Lysosomal Diseases Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IDUA Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

The NM_000203.5:c.439C>T (p.Gln147Ter) variant in IDUA is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 4 of 14 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has not been reported in the literature, but has been reported in ClinVar (Variation ID: 984179). This variant is absent from gnomAD v4.1.0. (PM2_Supporting). The ClinGen SVI recommendation for absence/rarity (PM2) suggests that the combination of PVS1 and PM2 should be considered as 'likely pathogenic'. Therefore this variant meets the criteria to be classified as likely pathogenic for MPS I based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 1.0.0.): PVS1, PM2_Supporting. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on December 5, 2024)

PVS1

The NM_000203.5:c.439C>T (p.Gln147Ter) variant in IDUA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4 out of 14, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 11735025, 21480867).

PM2_Supporting

This variant is absent from gnomAD v4.1.0. (PM2_Supporting).

PM3

This variant has not been reported in the literature to-date. There are two submissions regarding this variant in ClinVar, however neither confirm the patient's status as being affected by MPS I. Hence this criterion is not met.

PP4

There is insufficient detail provided in the two ClinVar submissions in order to apply this criterion.

Curation History

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