rs61733256

Positions:

chrX-2958302-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000047.3(ARSL):c.157A>G(p.Ile53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,210,149 control chromosomes in the GnomAD database, including 201 homozygotes. There are 1,810 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 Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 95 hom., 820 hem., cov: 23)

Exomes 𝑓: 0.0033 ( 106 hom. 990 hem. )

Consequence

ARSL
NM_000047.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.30

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=0.0037781894).

BP6

Variant X-2958302-T-C is Benign according to our data. Variant chrX-2958302-T-C is described in ClinVar as [Benign]. Clinvar id is 157729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSL	NM_000047.3 linkuse as main transcript	c.157A>G	p.Ile53Val	missense_variant	3/11	ENST00000381134.9	NP_000038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000381134.9 linkuse as main transcript	c.157A>G	p.Ile53Val	missense_variant	3/11	1	NM_000047.3	ENSP00000370526	P4

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

2984

AN:

111994

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

804

AN XY:

34160

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00483

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000244

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00837

AC:

1534

AN:

183171

Hom.:

AF XY:

0.00565

AC XY:

382

AN XY:

67615

show subpopulations

Gnomad AFR exome

AF:

0.0951

Gnomad AMR exome

AF:

0.00598

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.00432

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000232

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00329

AC:

3611

AN:

1098102

Hom.:

106

Cov.:

AF XY:

0.00272

AC XY:

990

AN XY:

363496

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00665

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.00807

GnomAD4 genome

AF:

0.0268

AC:

3008

AN:

112047

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

820

AN XY:

34223

show subpopulations

Gnomad4 AFR

AF:

0.0910

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00485

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000244

Gnomad4 OTH

AF:

0.0282

Alfa

AF:

0.00330

Hom.:

169

Bravo

AF:

0.0326

ESP6500AA

AF:

0.0988

AC:

379

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00923

AC:

1120

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 21, 2016	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. -

X-linked chondrodysplasia punctata 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.31

CADD

Benign

0.0010

DANN

Benign

0.23

DEOGEN2

Uncertain

0.51

D;T;.

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

-0.31

.;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.64

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.0050

MVP

0.69

MPC

0.37

ClinPred

0.0024

GERP RS

-7.2

Varity_R

0.039

gMVP

0.81

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