NM_000047.3:c.1728G>A

Variant names:

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.1728G>A(p.Pro576Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,182,636 control chromosomes in the GnomAD database, including 3,011 homozygotes. There are 27,622 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 189 hom., 1689 hem., cov: 22)

Exomes 𝑓: 0.074 ( 2822 hom. 25933 hem. )

Consequence

ARSL
NM_000047.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.21

Publications

4 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=-0.85).

BP6

Variant X-2934874-C-T is Benign according to our data. Variant chrX-2934874-C-T is described in ClinVar as Benign. ClinVar VariationId is 157731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSL	NM_000047.3 link	c.1728G>A	p.Pro576Pro	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.1728G>A	p.Pro576Pro	synonymous_variant	Exon 11 of 11	1	NM_000047.3	ENSP00000370526.3		P51690

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

6285

AN:

110925

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0719

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00847

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.0420

Gnomad NFE

AF:

0.0908

Gnomad OTH

AF:

0.0522

GnomAD2 exomes

AF:

0.0470

AC:

8196

AN:

174308

AF XY:

0.0372

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0212

Gnomad ASJ exome

AF:

0.0481

Gnomad EAS exome

AF:

0.0000729

Gnomad FIN exome

AF:

0.0626

Gnomad NFE exome

AF:

0.0752

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0739

AC:

79206

AN:

1071656

Hom.:

2822

Cov.:

AF XY:

0.0734

AC XY:

25933

AN XY:

353362

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0103

AC:

271

AN:

26202

American (AMR)

AF:

0.0249

AC:

862

AN:

34633

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

1173

AN:

18833

East Asian (EAS)

AF:

0.000200

AC:

AN:

30057

South Asian (SAS)

AF:

0.00915

AC:

484

AN:

52894

European-Finnish (FIN)

AF:

0.0698

AC:

2808

AN:

40238

Middle Eastern (MID)

AF:

0.0435

AC:

136

AN:

3128

European-Non Finnish (NFE)

AF:

0.0860

AC:

70528

AN:

820505

Other (OTH)

AF:

0.0650

AC:

2938

AN:

45166

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.357

Heterozygous variant carriers

2346

4692

7039

9385

11731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2512

5024

7536

10048

12560

<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:

0.0566

AC:

6283

AN:

110980

Hom.:

189

Cov.:

AF XY:

0.0509

AC XY:

1689

AN XY:

33184

show subpopulations

African (AFR)

AF:

0.0124

AC:

379

AN:

30652

American (AMR)

AF:

0.0408

AC:

424

AN:

10403

Ashkenazi Jewish (ASJ)

AF:

0.0719

AC:

189

AN:

2627

East Asian (EAS)

AF:

0.00

AC:

AN:

3524

South Asian (SAS)

AF:

0.00850

AC:

AN:

2588

European-Finnish (FIN)

AF:

0.0606

AC:

358

AN:

5912

Middle Eastern (MID)

AF:

0.0459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0908

AC:

4799

AN:

52862

Other (OTH)

AF:

0.0516

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

215

431

646

862

1077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0667

Hom.:

569

Bravo

AF:

0.0529

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.069

(source)

DANN

Benign

0.48

PhyloP100

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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