5-78985092-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The ENST00000264914.10(ARSB):c.157G>A(p.Asp53Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D53G) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000264914.10 missense
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.157G>A | p.Asp53Asn | missense_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.157G>A | p.Asp53Asn | missense_variant | 1/8 | 1 | NM_000046.5 | ENSP00000264914 | P1 | |
ARSB | ENST00000396151.7 | c.157G>A | p.Asp53Asn | missense_variant | 2/8 | 1 | ENSP00000379455 | |||
ARSB | ENST00000565165.2 | c.157G>A | p.Asp53Asn | missense_variant | 1/5 | 1 | ENSP00000456339 | |||
ARSB | ENST00000521117.1 | downstream_gene_variant | 3 | ENSP00000428611 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1376298Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 681984
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics | Dec 24, 2022 | A heterozygous missense variation in exon 1 of ARSB gene that results in amino acid substitution of Aspargine for Aspartic acid at codon 53 was detected. The observed variant c.157G>A (p.Asp53Asn) has not been reported in the 1000 genomes and gnomAD databases. The in-silico predictions for the variant is disease causing by MutationTaster2, SIFT and PROVEAN. In summary, the variant is pathogenic. - |
Likely pathogenic, criteria provided, single submitter | curation | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jan 01, 2018 | In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3);Located in a well-established functional domain (PM1); Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3); - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at