rs199476382
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_000487.6(ARSA):c.938G>T(p.Arg313Leu) variant causes a missense change. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R313P) has been classified as Pathogenic.
Frequency
Consequence
NM_000487.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARSA | NM_000487.6 | c.938G>T | p.Arg313Leu | missense_variant | Exon 5 of 8 | ENST00000216124.10 | NP_000478.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARSA | ENST00000216124.10 | c.938G>T | p.Arg313Leu | missense_variant | Exon 5 of 8 | 1 | NM_000487.6 | ENSP00000216124.5 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458570Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 725370
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Metachromatic leukodystrophy Uncertain:2
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.98; 3Cnet: 1.00). Different missense changes at the same codon (p.Arg313Gln, p.Arg313Gly, p.Arg313Pro) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000068165 / PMID: 26462614, 34490615, 7581401). Therefore, this variant is classified as Uncertain significance according to the recommendation of ACMG/AMP guideline. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.