rs1554032090
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000046.5(ARSB):c.293T>G(p.Leu98Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000758 in 1,319,688 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L98P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000046.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.293T>G | p.Leu98Arg | missense_variant | 1/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.293T>G | p.Leu98Arg | missense_variant | 1/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.293T>G | p.Leu98Arg | missense_variant | 2/8 | 1 | |||
ARSB | ENST00000565165.2 | c.293T>G | p.Leu98Arg | missense_variant | 1/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 151550Hom.: 0 Cov.: 33 FAILED QC
GnomAD4 exome AF: 7.58e-7 AC: 1AN: 1319688Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1AN XY: 652988
GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 151550Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74008
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | curation | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jan 01, 2018 | In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at