Variant rs11222 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.1692C>T(p.Asn564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 110,155 control chromosomes in the GnomAD database, including 11,591 homozygotes. There are 16,122 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 11591 hom., 16122 hem., cov: 22)

Exomes 𝑓: 0.62 ( 143441 hom. 227173 hem. )

Failed GnomAD Quality Control

Consequence

ARSL
NM_000047.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.289

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=-0.84).

BP6

Variant X-2934910-G-A is Benign according to our data. Variant chrX-2934910-G-A is described in ClinVar as [Benign]. Clinvar id is 157730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2934910-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.289 with no splicing effect.

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	UniProt
ARSL	NM_000047.3 linkuse as main transcript	c.1692C>T	p.Asn564=	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.1692C>T	p.Asn564=	synonymous_variant	11/11	1	NM_000047.3	P4

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

54718

AN:

110104

Hom.:

11601

Cov.:

AF XY:

0.498

AC XY:

16121

AN XY:

32354

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.717

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.810

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.535

GnomAD3 exomes

AF:

0.624

AC:

109395

AN:

175426

Hom.:

23483

AF XY:

0.638

AC XY:

38868

AN XY:

60920

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.897

Gnomad SAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.645

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.624

AC:

677668

AN:

1086506

Hom.:

143441

Cov.:

AF XY:

0.634

AC XY:

227173

AN XY:

358128

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.724

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.808

Gnomad4 FIN exome

AF:

0.595

Gnomad4 NFE exome

AF:

0.619

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.497

AC:

54693

AN:

110155

Hom.:

11591

Cov.:

AF XY:

0.497

AC XY:

16122

AN XY:

32415

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.717

Gnomad4 EAS

AF:

0.878

Gnomad4 SAS

AF:

0.810

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.588

Hom.:

7020

Bravo

AF:

0.482

ClinVar

Significance: Benign

Submissions summary: Benign:7

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	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

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	-	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

X-linked chondrodysplasia punctata 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.96

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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