rs1554032095
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000046.5(ARSB):āc.288C>Gā(p.Ser96Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000151 in 1,327,278 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S96G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000046.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.288C>G | p.Ser96Arg | missense_variant | 1/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.288C>G | p.Ser96Arg | missense_variant | 1/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.288C>G | p.Ser96Arg | missense_variant | 2/8 | 1 | |||
ARSB | ENST00000565165.2 | c.288C>G | p.Ser96Arg | missense_variant | 1/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000151 AC: 2AN: 1327278Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1AN XY: 657324
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:1Uncertain: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) - |
Pathogenic, criteria provided, single submitter | research | Medical Molecular Genetics Department, National Research Center | Dec 01, 2015 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2021 | Variant summary: ARSB c.288C>G (p.Ser96Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 142908 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.288C>G has been reported in the literature in one individual affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome). This report does 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at