Variant X-2949372-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.786G>A(p.Thr262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 1,208,970 control chromosomes in the GnomAD database, including 2,596 homozygotes. There are 28,239 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 186 hom., 1899 hem., cov: 22)

Exomes 𝑓: 0.074 ( 2410 hom. 26340 hem. )

Consequence

ARSL
NM_000047.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.83

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-2949372-C-T is Benign according to our data. Variant chrX-2949372-C-T is described in ClinVar as [Benign]. Clinvar id is 157736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-2949372-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0922 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.786G>A	p.Thr262=	synonymous_variant	6/11	ENST00000381134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSL	ENST00000381134.9 linkuse as main transcript	c.786G>A	p.Thr262=	synonymous_variant	6/11	1	NM_000047.3	P4

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

6530

AN:

110786

Hom.:

187

Cov.:

AF XY:

0.0576

AC XY:

1901

AN XY:

33016

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0659

Gnomad AMR

AF:

0.0974

Gnomad ASJ

AF:

0.0774

Gnomad EAS

AF:

0.000565

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0718

Gnomad MID

AF:

0.0750

Gnomad NFE

AF:

0.0822

Gnomad OTH

AF:

0.0533

GnomAD3 exomes

AF:

0.0784

AC:

14357

AN:

183226

Hom.:

563

AF XY:

0.0709

AC XY:

4796

AN XY:

67674

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.0749

Gnomad EAS exome

AF:

0.0000721

Gnomad SAS exome

AF:

0.0301

Gnomad FIN exome

AF:

0.0725

Gnomad NFE exome

AF:

0.0814

Gnomad OTH exome

AF:

0.0770

GnomAD4 exome

AF:

0.0744

AC:

81648

AN:

1098133

Hom.:

2410

Cov.:

AF XY:

0.0725

AC XY:

26340

AN XY:

363491

show subpopulations

Gnomad4 AFR exome

AF:

0.00864

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.0780

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0319

Gnomad4 FIN exome

AF:

0.0752

Gnomad4 NFE exome

AF:

0.0783

Gnomad4 OTH exome

AF:

0.0646

GnomAD4 genome

AF:

0.0588

AC:

6522

AN:

110837

Hom.:

186

Cov.:

AF XY:

0.0574

AC XY:

1899

AN XY:

33077

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.0972

Gnomad4 ASJ

AF:

0.0774

Gnomad4 EAS

AF:

0.000567

Gnomad4 SAS

AF:

0.0285

Gnomad4 FIN

AF:

0.0718

Gnomad4 NFE

AF:

0.0822

Gnomad4 OTH

AF:

0.0527

Alfa

AF:

0.0828

Hom.:

1382

Bravo

AF:

0.0624

EpiCase

AF:

0.0790

EpiControl

AF:

0.0783

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 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	- -

Chondrodysplasia punctata, brachytelephalangic, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.037

DANN

Benign

0.49

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