rs34412194

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000047.3(ARSL):c.548G>A(p.Arg183His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,209,010 control chromosomes in the GnomAD database, including 46 homozygotes. There are 1,495 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 18 hom., 341 hem., cov: 22)

Exomes 𝑓: 0.0036 ( 28 hom. 1154 hem. )

Consequence

ARSL
NM_000047.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.67

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050126314).

BP6

Variant X-2949610-C-T is Benign according to our data. Variant chrX-2949610-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 157734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2949610-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1420/110837) while in subpopulation AFR AF= 0.0385 (1173/30460). AF 95% confidence interval is 0.0367. There are 18 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSL	NM_000047.3 link	c.548G>A	p.Arg183His	missense_variant	Exon 6 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.548G>A	p.Arg183His	missense_variant	Exon 6 of 11	1	NM_000047.3	ENSP00000370526.3		P51690

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1417

AN:

110783

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

339

AN XY:

33005

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00502

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00334

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00426

AC:

780

AN:

183199

Hom.:

AF XY:

0.00324

AC XY:

219

AN XY:

67657

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00364

AC:

3999

AN:

1098173

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

1154

AN XY:

363529

show subpopulations

Gnomad4 AFR exome

AF:

0.0407

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.000222

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.0128

AC:

1420

AN:

110837

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

341

AN XY:

33069

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.00501

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.00334

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00388

Hom.:

132

Bravo

AF:

0.0141

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00312

AC:

ESP6500AA

AF:

0.0389

AC:

149

ESP6500EA

AF:

0.00297

AC:

ExAC

AF:

0.00474

AC:

575

EpiCase

AF:

0.00224

EpiControl

AF:

0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 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	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 04, 2015	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2025

- -

X-linked chondrodysplasia punctata 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 28, 2023

- -

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.0020

DANN

Benign

0.86

DEOGEN2

Uncertain

0.46

T;.;T

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.12

T;T;T

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Uncertain

-0.052

MutationAssessor

Benign

-0.38

.;.;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.019

MVP

0.86

MPC

0.55

ClinPred

0.0060

GERP RS

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over