rs1554087999
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000046.5(ARSB):c.499G>A(p.Gly167Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 16/25 in silico tools predict a damaging outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. G167G) has been classified as Likely benign.
Frequency
Consequence
NM_000046.5 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.499G>A | p.Gly167Arg | missense_variant, splice_region_variant | 2/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.499G>A | p.Gly167Arg | missense_variant, splice_region_variant | 2/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.499G>A | p.Gly167Arg | missense_variant, splice_region_variant | 3/8 | 1 | |||
ARSB | ENST00000565165.2 | c.499G>A | p.Gly167Arg | missense_variant, splice_region_variant | 2/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74302
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 10, 2023 | - - |
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