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rs122460154

Positions:

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000047.3(ARSL):​c.733G>C​(p.Gly245Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

ARSL
NM_000047.3 missense

Scores

3
5
8

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.0440
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974
PP5
Variant X-2949425-C-G is Pathogenic according to our data. Variant chrX-2949425-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 11526.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-2949425-C-G is described in Lovd as [Pathogenic]. Variant chrX-2949425-C-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARSLNM_000047.3 linkuse as main transcriptc.733G>C p.Gly245Arg missense_variant 6/11 ENST00000381134.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARSLENST00000381134.9 linkuse as main transcriptc.733G>C p.Gly245Arg missense_variant 6/111 NM_000047.3 P4

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

X-linked chondrodysplasia punctata 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 07, 1995- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
7.8
DANN
Benign
0.53
DEOGEN2
Uncertain
0.46
T;.;T
FATHMM_MKL
Benign
0.047
N
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Pathogenic
0.59
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Uncertain
-0.034
T
MutationTaster
Benign
8.9e-13
A;A;A
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Uncertain
0.58
Sift
Benign
0.35
T;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.020
B;B;B
Vest4
0.76
MutPred
0.62
Loss of sheet (P = 0.0037);.;.;
MVP
0.93
MPC
1.4
ClinPred
0.14
T
GERP RS
0.16
Varity_R
0.16
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs122460154; hg19: chrX-2867466; API