Variant rs80338711 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5

The ENST00000381134.9(ARSL):c.410G>T(p.Gly137Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 112,469 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G137A) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Consequence

ARSL
ENST00000381134.9 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.61

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 Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrX-2953163-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 21033.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=4, Uncertain_significance=2, not_provided=1}.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.993

PP5

Variant X-2953163-C-A is Pathogenic according to our data. Variant chrX-2953163-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11525.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-2953163-C-A is described in Lovd as [Pathogenic]. Variant chrX-2953163-C-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSL	NM_000047.3 linkuse as main transcript	c.410G>T	p.Gly137Val	missense_variant	5/11	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.410G>T	p.Gly137Val	missense_variant	5/11	1	NM_000047.3	ENSP00000370526	P4

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34625

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34625

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

X-linked chondrodysplasia punctata 1

Pathogenic:1Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 07, 1995	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.70

BayesDel_noAF

Pathogenic

0.76

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;.;D;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.99

D;D;D;D

MetaSVM

Pathogenic

0.95

MutationAssessor

Pathogenic

4.6

.;.;H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-8.9

D;D;D;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

1.0

D;D;D;.

Vest4

0.94

MutPred

0.93

Loss of disorder (P = 0.0702);.;.;.;

MVP

0.98

MPC

1.5

ClinPred

1.0

GERP RS

3.5

Varity_R

0.92

gMVP

1.0

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