Variant X-2934874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000047.3(ARSL):c.1728G>A(p.Pro576=) 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:4

Conservation

PhyloP100: -3.21

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ARSL	NM_000047.3 linkuse as main transcript	c.1728G>A	p.Pro576=	synonymous_variant	11/11	ENST00000381134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSL	ENST00000381134.9 linkuse as main transcript	c.1728G>A	p.Pro576=	synonymous_variant	11/11	1	NM_000047.3	P4

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

6285

AN:

110925

Hom.:

189

Cov.:

AF XY:

0.0510

AC XY:

1689

AN XY:

33119

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

GnomAD3 exomes

AF:

0.0470

AC:

8196

AN:

174308

Hom.:

223

AF XY:

0.0372

AC XY:

2234

AN XY:

60022

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 SAS exome

AF:

0.00740

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

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.0623

Gnomad4 EAS exome

AF:

0.000200

Gnomad4 SAS exome

AF:

0.00915

Gnomad4 FIN exome

AF:

0.0698

Gnomad4 NFE exome

AF:

0.0860

Gnomad4 OTH exome

AF:

0.0650

GnomAD4 genome

AF:

0.0566

AC:

6283

AN:

110980

Hom.:

189

Cov.:

AF XY:

0.0509

AC XY:

1689

AN XY:

33184

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.0408

Gnomad4 ASJ

AF:

0.0719

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.0606

Gnomad4 NFE

AF:

0.0908

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.0667

Hom.:

569

Bravo

AF:

0.0529

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

0.069

Dann

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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