rs6151412
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000487.6(ARSA):c.459C>T(p.His153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,611,236 control chromosomes in the GnomAD database, including 1,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.056 ( 310 hom., cov: 33)
Exomes 𝑓: 0.042 ( 1628 hom. )
Consequence
ARSA
NM_000487.6 synonymous
NM_000487.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.474
Genes affected
ARSA (HGNC:713): (arylsulfatase A) The protein encoded by this gene hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in this gene lead to metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in a variety of neurological symptoms and ultimately death. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 22-50627172-G-A is Benign according to our data. Variant chr22-50627172-G-A is described in ClinVar as [Benign]. Clinvar id is 93123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50627172-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.474 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSA | NM_000487.6 | c.459C>T | p.His153= | synonymous_variant | 2/8 | ENST00000216124.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSA | ENST00000216124.10 | c.459C>T | p.His153= | synonymous_variant | 2/8 | 1 | NM_000487.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0561 AC: 8540AN: 152182Hom.: 309 Cov.: 33
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GnomAD3 exomes AF: 0.0338 AC: 8139AN: 240752Hom.: 235 AF XY: 0.0329 AC XY: 4335AN XY: 131692
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GnomAD4 exome AF: 0.0422 AC: 61597AN: 1458936Hom.: 1628 Cov.: 33 AF XY: 0.0409 AC XY: 29689AN XY: 725454
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GnomAD4 genome ? AF: 0.0561 AC: 8548AN: 152300Hom.: 310 Cov.: 33 AF XY: 0.0530 AC XY: 3946AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 24, 2013 | - - |
Metachromatic leukodystrophy Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 29, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 18, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Citrullinemia Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at