X-2938114-C-T

Position:

chrX-2938114-C-T

Variant summary

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

The NM_000047.3(ARSL):c.1270G>A(p.Gly424Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 110,753 control chromosomes in the GnomAD database, including 12,948 homozygotes. There are 17,389 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 12948 hom., 17389 hem., cov: 23)

Exomes 𝑓: 0.66 ( 162105 hom. 244944 hem. )

Failed GnomAD Quality Control

Consequence

ARSL
NM_000047.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.69

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:

ARSL (HGNC:):

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=1.2959954E-6).

BP6

Variant X-2938114-C-T is Benign according to our data. Variant chrX-2938114-C-T is described in ClinVar as [Benign]. Clinvar id is 157728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2938114-C-T is described in Lovd as [Benign].

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	Protein	UniProt
ARSL	NM_000047.3 linkuse as main transcript	c.1270G>A	p.Gly424Ser	missense_variant	9/11	ENST00000381134.9	NP_000038.2	P51690

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000381134.9 linkuse as main transcript	c.1270G>A	p.Gly424Ser	missense_variant	9/11	1	NM_000047.3	ENSP00000370526.3		P51690

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

58222

AN:

110700

Hom.:

12959

Cov.:

AF XY:

0.528

AC XY:

17390

AN XY:

32924

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.795

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.739

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.755

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.555

GnomAD3 exomes

AF:

0.658

AC:

119558

AN:

181573

Hom.:

25425

AF XY:

0.684

AC XY:

45870

AN XY:

67035

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.595

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.896

Gnomad SAS exome

AF:

0.829

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.677

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.663

AC:

727532

AN:

1097883

Hom.:

162105

Cov.:

AF XY:

0.674

AC XY:

244944

AN XY:

363365

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.747

Gnomad4 EAS exome

AF:

0.861

Gnomad4 SAS exome

AF:

0.824

Gnomad4 FIN exome

AF:

0.626

Gnomad4 NFE exome

AF:

0.664

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.525

AC:

58193

AN:

110753

Hom.:

12948

Cov.:

AF XY:

0.527

AC XY:

17389

AN XY:

32987

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.739

Gnomad4 EAS

AF:

0.878

Gnomad4 SAS

AF:

0.822

Gnomad4 FIN

AF:

0.614

Gnomad4 NFE

AF:

0.673

Gnomad4 OTH

AF:

0.552

Alfa

AF:

0.588

Hom.:

8806

Bravo

AF:

0.506

TwinsUK

AF:

0.659

AC:

2442

ALSPAC

AF:

0.661

AC:

1909

ESP6500AA

AF:

0.179

AC:

687

ESP6500EA

AF:

0.671

AC:

4504

ExAC

AF:

0.664

AC:

80566

EpiCase

AF:

0.683

EpiControl

AF:

0.686

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	- -

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	- -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.77

D;.;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0000013

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.94

P;P;P

Vest4

0.090

MPC

1.3

ClinPred

0.036

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.92

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