rs746206847
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PS1_Very_StrongPM1PM2PP3_StrongPP5_Moderate
The NM_000046.5(ARSB):c.430G>C(p.Gly144Arg) 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. 13/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Synonymous variant affecting the same amino acid position (i.e. G144G) has been classified as Likely benign.
Frequency
Consequence
NM_000046.5 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 | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.430G>C | p.Gly144Arg | missense_variant | 2/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.430G>C | p.Gly144Arg | missense_variant | 2/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.430G>C | p.Gly144Arg | missense_variant | 3/8 | 1 | |||
ARSB | ENST00000565165.2 | c.430G>C | p.Gly144Arg | missense_variant | 2/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2020 | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. A different variant (c.430G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 8116615, 30982216, 16435196, 26909334). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 144 of the ARSB protein (p.Gly144Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.