rs771296632
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000046.5(ARSB):c.1208C>T(p.Ser403Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S403S) has been classified as Likely benign.
Frequency
Consequence
NM_000046.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSB | NM_000046.5 | c.1208C>T | p.Ser403Leu | missense_variant | 6/8 | ENST00000264914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSB | ENST00000264914.10 | c.1208C>T | p.Ser403Leu | missense_variant | 6/8 | 1 | NM_000046.5 | P1 | |
ARSB | ENST00000396151.7 | c.1208C>T | p.Ser403Leu | missense_variant | 7/8 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251352Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461344Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 726996
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2021 | This sequence change replaces serine, a(n) neutral and polar amino acid, with leucine, a(n) neutral and non-polar amino acid, at codon 403 of the ARSB protein (p.Ser403Leu). This variant is present in population databases (rs771296632, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ARSB-related conditions. 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 not expected to disrupt ARSB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at