rs11222

chrX-2934910-G-AchrX-2934910-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000047.3(ARSL):c.1692C>T(p.Asn564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 110,155 control chromosomes in the GnomAD database, including 11,591 homozygotes. There are 16,122 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (11591 hom., 16122 hem., cov: 22)
  • Exomes 𝑓: 0.62 (143441 hom. 227173 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARSL NM_000047.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.289

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-2934910-G-A is Benign according to our data. Variant chrX-2934910-G-A is described in ClinVar as [Benign]. Clinvar id is 157730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2934910-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.289 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSL	NM_000047.3	c.1692C>T	p.Asn564=	synonymous_variant	11/11	ENST00000381134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSL	ENST00000381134.9	c.1692C>T	p.Asn564=	synonymous_variant	11/11	1	NM_000047.3	P4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 54718 AN: 110104 Hom.: 11601 Cov.: 22 AF XY: 0.498 AC XY: 16121 AN XY: 32354

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.624 AC: 109395 AN: 175426 Hom.: 23483 AF XY: 0.638 AC XY: 38868 AN XY: 60920

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.897

Gnomad SAS exome AF: 0.807

Gnomad FIN exome AF: 0.590

Gnomad NFE exome AF: 0.625

Gnomad OTH exome AF: 0.645

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.624 AC: 677668 AN: 1086506 Hom.: 143441 Cov.: 36 AF XY: 0.634 AC XY: 227173 AN XY: 358128

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.619

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.497 AC: 54693 AN: 110155 Hom.: 11591 Cov.: 22 AF XY: 0.497 AC XY: 16122 AN XY: 32415

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.533

Alfa AF: 0.588 Hom.: 7020

Bravo AF: 0.482

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 19, 2015	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

X-linked chondrodysplasia punctata 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.96
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11222; hg19: chrX-2852951; COSMIC: COSV66965761;