X-2960404-GTCTC-GTCTCTC
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 10P and 2B. PVS1PM2BP6_Moderate
The NM_001369079.1(ARSL):c.22_23dupGA(p.Asp8GlufsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,425 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 20)
Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )
Consequence
ARSL
NM_001369079.1 frameshift
NM_001369079.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.26
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- X-linked chondrodysplasia punctata 1Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 39 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant X-2960404-G-GTC is Benign according to our data. Variant chrX-2960404-G-GTC is described in ClinVar as Benign. ClinVar VariationId is 1686515.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001369079.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ARSL | NM_000047.3 | MANE Select | c.-6_-5dupGA | 5_prime_UTR | Exon 2 of 11 | NP_000038.2 | |||
| ARSL | NM_001369079.1 | c.22_23dupGA | p.Asp8GlufsTer26 | frameshift | Exon 2 of 11 | NP_001356008.1 | |||
| ARSL | NM_001282628.2 | c.-217_-216dupGA | 5_prime_UTR | Exon 2 of 12 | NP_001269557.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ARSL | ENST00000381134.9 | TSL:1 MANE Select | c.-6_-5dupGA | 5_prime_UTR | Exon 2 of 11 | ENSP00000370526.3 | |||
| ARSL | ENST00000545496.6 | TSL:2 | c.-217_-216dupGA | 5_prime_UTR | Exon 2 of 12 | ENSP00000441417.1 | |||
| ARSL | ENST00000672027.1 | c.-217_-216dupGA | 5_prime_UTR | Exon 2 of 12 | ENSP00000500220.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
20
GnomAD4 exome AF: 9.23e-7 AC: 1AN: 1083425Hom.: 0 Cov.: 28 AF XY: 0.00000284 AC XY: 1AN XY: 351497 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1083425
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
351497
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26126
American (AMR)
AF:
AC:
0
AN:
34978
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19068
East Asian (EAS)
AF:
AC:
0
AN:
29802
South Asian (SAS)
AF:
AC:
0
AN:
53792
European-Finnish (FIN)
AF:
AC:
0
AN:
38855
Middle Eastern (MID)
AF:
AC:
0
AN:
4080
European-Non Finnish (NFE)
AF:
AC:
0
AN:
831284
Other (OTH)
AF:
AC:
1
AN:
45440
Age Distribution
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
20
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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