rs775536824
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000487.6(ARSA):c.224+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,560,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000487.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSA | NM_000487.6 | c.224+8G>A | splice_region_variant, intron_variant | ENST00000216124.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSA | ENST00000216124.10 | c.224+8G>A | splice_region_variant, intron_variant | 1 | NM_000487.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151778Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000423 AC: 7AN: 165656Hom.: 0 AF XY: 0.0000451 AC XY: 4AN XY: 88778
GnomAD4 exome AF: 0.0000163 AC: 23AN: 1408554Hom.: 0 Cov.: 32 AF XY: 0.0000172 AC XY: 12AN XY: 695940
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151896Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74296
ClinVar
Submissions by phenotype
Metachromatic leukodystrophy Benign:1Other:1
not provided, no classification provided | in vitro | Gelb Laboratory, University of Washington | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
ARSA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 22, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at