rs1236509896
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_000046.5(ARSB):c.175G>A(p.Asp59Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,391,952 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D59G) 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 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.175G>A | p.Asp59Asn | missense_variant | 1/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.175G>A | p.Asp59Asn | missense_variant | 1/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.175G>A | p.Asp59Asn | missense_variant | 2/8 | 1 | |||
ARSB | ENST00000565165.2 | c.175G>A | p.Asp59Asn | missense_variant | 1/5 | 1 | |||
ARSB | ENST00000521117.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000144 AC: 2AN: 1391952Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 691800
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 11, 2023 | Variant summary: ARSB c.175G>A (p.Asp59Asn) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182070 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.175G>A has been reported in the literature in the heterozygous state in two Brazilian individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (Petry_2005, Horovitz_2015). These reports do not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28649537, 16435196). One submitter has provided a clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Mucopolysaccharidosis type 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jan 01, 2018 | Absent from GnomAD (PM2); - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at