rs747981483
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_000203.5(IDUA):c.236C>T(p.Ala79Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A79T) has been classified as Likely benign.
Frequency
Consequence
NM_000203.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDUA | NM_000203.5 | c.236C>T | p.Ala79Val | missense_variant | 2/14 | ENST00000514224.2 | |
SLC26A1 | NM_022042.4 | c.*947G>A | 3_prime_UTR_variant | 3/3 | ENST00000398516.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.236C>T | p.Ala79Val | missense_variant | 2/14 | 2 | NM_000203.5 | P1 | |
SLC26A1 | ENST00000398516.3 | c.*947G>A | 3_prime_UTR_variant | 3/3 | 1 | NM_022042.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000420 AC: 1AN: 238030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129756
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2022 | Experimental studies have shown that this missense change affects IDUA function (PMID: 12189649). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1458769). This missense change has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 15300847, 21462124, 21734815). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 79 of the IDUA protein (p.Ala79Val). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 19, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at