rs17325750
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000047.3(ARSL):c.786G>A(p.Thr262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 1,208,970 control chromosomes in the GnomAD database, including 2,596 homozygotes. There are 28,239 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.059 ( 186 hom., 1899 hem., cov: 22)
Exomes 𝑓: 0.074 ( 2410 hom. 26340 hem. )
Consequence
ARSL
NM_000047.3 synonymous
NM_000047.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.83
Genes affected
ARSL (HGNC:719): (arylsulfatase L) Arylsulfatase E is a member of the sulfatase family. It is glycosylated postranslationally and localized to the golgi apparatus. Sulfatases are essential for the correct composition of bone and cartilage matrix. X-linked chondrodysplasia punctata, a disease characterized by abnormalities in cartilage and bone development, has been linked to mutations in this gene. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the Y chromosome. [provided by RefSeq, Sep 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant X-2949372-C-T is Benign according to our data. Variant chrX-2949372-C-T is described in ClinVar as [Benign]. Clinvar id is 157736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2949372-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.83 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSL | NM_000047.3 | c.786G>A | p.Thr262= | synonymous_variant | 6/11 | ENST00000381134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSL | ENST00000381134.9 | c.786G>A | p.Thr262= | synonymous_variant | 6/11 | 1 | NM_000047.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0589 AC: 6530AN: 110786Hom.: 187 Cov.: 22 AF XY: 0.0576 AC XY: 1901AN XY: 33016
GnomAD3 genomes
AF:
AC:
6530
AN:
110786
Hom.:
Cov.:
22
AF XY:
AC XY:
1901
AN XY:
33016
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0784 AC: 14357AN: 183226Hom.: 563 AF XY: 0.0709 AC XY: 4796AN XY: 67674
GnomAD3 exomes
AF:
AC:
14357
AN:
183226
Hom.:
AF XY:
AC XY:
4796
AN XY:
67674
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0744 AC: 81648AN: 1098133Hom.: 2410 Cov.: 32 AF XY: 0.0725 AC XY: 26340AN XY: 363491
GnomAD4 exome
AF:
AC:
81648
AN:
1098133
Hom.:
Cov.:
32
AF XY:
AC XY:
26340
AN XY:
363491
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0588 AC: 6522AN: 110837Hom.: 186 Cov.: 22 AF XY: 0.0574 AC XY: 1899AN XY: 33077
GnomAD4 genome
AF:
AC:
6522
AN:
110837
Hom.:
Cov.:
22
AF XY:
AC XY:
1899
AN XY:
33077
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Chondrodysplasia punctata, brachytelephalangic, autosomal Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at