rs1554032094
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000046.5(ARSB):c.289C>T(p.Gln97Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000754 in 1,326,384 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000046.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.289C>T | p.Gln97Ter | stop_gained | 1/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.289C>T | p.Gln97Ter | stop_gained | 1/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.289C>T | p.Gln97Ter | stop_gained | 2/8 | 1 | |||
ARSB | ENST00000565165.2 | c.289C>T | p.Gln97Ter | stop_gained | 1/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 7.54e-7 AC: 1AN: 1326384Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 656826
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 16, 2023 | This sequence change creates a premature translational stop signal (p.Gln97*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 559762). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 14974081). This variant is not present in population databases (gnomAD no frequency). - |
Likely pathogenic, criteria provided, single submitter | curation | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jan 01, 2018 | Nonsense variant (PVS1); Absent from GnomAD (PM2) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at