rs11222

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000047.3(ARSL):c.1692C>T(p.Asn564Asn) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.289

Publications

16 publications found

Variant links:

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]

ARSL Gene-Disease associations (from GenCC):

X-linked chondrodysplasia punctata 1
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ARSL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 157730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ARSL	NM_000047.3 link	c.1692C>T	p.Asn564Asn	synonymous_variant	Exon 11 of 11	ENST00000381134.9	NP_000038.2	P51690

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000381134.9 link	c.1692C>T	p.Asn564Asn	synonymous_variant	Exon 11 of 11	1	NM_000047.3	ENSP00000370526.3		P51690

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

54718

AN:

110104

Hom.:

11601

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.624

AC:

109395

AN:

175426

AF XY:

0.638

show subpopulations

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 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.:

AF XY:

0.634

AC XY:

227173

AN XY:

358128

show subpopulations

African (AFR)

AF:

0.144

AC:

3786

AN:

26285

American (AMR)

AF:

0.578

AC:

20123

AN:

34791

Ashkenazi Jewish (ASJ)

AF:

0.724

AC:

13839

AN:

19111

East Asian (EAS)

AF:

0.862

AC:

25933

AN:

30102

South Asian (SAS)

AF:

0.808

AC:

43311

AN:

53586

European-Finnish (FIN)

AF:

0.595

AC:

23959

AN:

40294

Middle Eastern (MID)

AF:

0.713

AC:

2515

AN:

3529

European-Non Finnish (NFE)

AF:

0.619

AC:

515957

AN:

833181

Other (OTH)

AF:

0.619

AC:

28245

AN:

45627

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

7977

15954

23931

31908

39885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15860

31720

47580

63440

79300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.497

AC:

54693

AN:

110155

Hom.:

11591

Cov.:

AF XY:

0.497

AC XY:

16122

AN XY:

32415

show subpopulations

African (AFR)

AF:

0.154

AC:

4691

AN:

30557

American (AMR)

AF:

0.522

AC:

5373

AN:

10300

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

1877

AN:

2619

East Asian (EAS)

AF:

0.878

AC:

3031

AN:

3452

South Asian (SAS)

AF:

0.810

AC:

2038

AN:

2516

European-Finnish (FIN)

AF:

0.580

AC:

3333

AN:

5744

Middle Eastern (MID)

AF:

0.730

AC:

157

AN:

215

European-Non Finnish (NFE)

AF:

0.626

AC:

32900

AN:

52589

Other (OTH)

AF:

0.533

AC:

797

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

801

1602

2404

3205

4006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.588

Hom.:

7020

Bravo

AF:

0.482

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 19, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

X-linked chondrodysplasia punctata 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.96

(source)

DANN

Benign

0.49

PhyloP100

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over