rs750845916
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000264914.10(ARSB):βc.245delβ(p.Leu82ArgfsTer32) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000577 in 1,387,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. L82L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000264914.10 frameshift
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.245del | p.Leu82ArgfsTer32 | frameshift_variant | 1/8 | ENST00000264914.10 | NP_000037.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.245del | p.Leu82ArgfsTer32 | frameshift_variant | 1/8 | 1 | NM_000046.5 | ENSP00000264914 | P1 | |
ARSB | ENST00000396151.7 | c.245del | p.Leu82ArgfsTer32 | frameshift_variant | 2/8 | 1 | ENSP00000379455 | |||
ARSB | ENST00000565165.2 | c.245del | p.Leu82ArgfsTer32 | frameshift_variant | 1/5 | 1 | ENSP00000456339 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000567 AC: 1AN: 176244Hom.: 0 AF XY: 0.0000100 AC XY: 1AN XY: 99946
GnomAD4 exome AF: 0.00000577 AC: 8AN: 1387590Hom.: 0 Cov.: 31 AF XY: 0.00000725 AC XY: 5AN XY: 689762
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 07, 2022 | This sequence change creates a premature translational stop signal (p.Leu82Argfs*32) 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). This variant is present in population databases (rs750845916, gnomAD 0.001%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 559746). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 10923267). - |
Likely pathogenic, criteria provided, single submitter | curation | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jan 01, 2018 | Frameshift variant (PVS1); Very low frequence in GnomAd (PM2) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at