chrX-41123703-G-GC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001039591.3(USP9X):c.82dupC(p.Leu28ProfsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
USP9X
NM_001039591.3 frameshift
NM_001039591.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.57
Publications
1 publications found
Genes affected
USP9X (HGNC:12632): (ubiquitin specific peptidase 9 X-linked) This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
USP9X Gene-Disease associations (from GenCC):
- intellectual disability, X-linked 99, syndromic, female-restrictedInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- X-linked syndromic intellectual disabilityInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- intellectual disability, X-linked 99Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- non-syndromic X-linked intellectual disabilityInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disabilityInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 113 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-41123703-G-GC is Pathogenic according to our data. Variant chrX-41123703-G-GC is described in ClinVar as Pathogenic. ClinVar VariationId is 1254438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001039591.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| USP9X | MANE Select | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 2 of 45 | NP_001034680.2 | Q93008-1 | ||
| USP9X | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 3 of 46 | NP_001397677.1 | A0A994J4R6 | |||
| USP9X | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 2 of 45 | NP_001034679.2 | Q93008-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| USP9X | TSL:5 MANE Select | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 2 of 45 | ENSP00000367558.2 | Q93008-1 | ||
| USP9X | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 2 of 45 | ENSP00000515604.1 | A0A994J4R6 | |||
| USP9X | TSL:5 | c.82dupC | p.Leu28ProfsTer10 | frameshift | Exon 2 of 45 | ENSP00000316357.6 | Q93008-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD2 exomes AF: 0.00 AC: 0AN: 179139 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
179139
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1097625Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 362993
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1097625
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
362993
African (AFR)
AF:
AC:
0
AN:
26382
American (AMR)
AF:
AC:
0
AN:
35162
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19357
East Asian (EAS)
AF:
AC:
0
AN:
30179
South Asian (SAS)
AF:
AC:
0
AN:
54050
European-Finnish (FIN)
AF:
AC:
0
AN:
40516
Middle Eastern (MID)
AF:
AC:
0
AN:
4134
European-Non Finnish (NFE)
AF:
AC:
0
AN:
841771
Other (OTH)
AF:
AC:
0
AN:
46074
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
not provided (2)
1
-
-
Inborn genetic diseases (1)
1
-
-
USP9X-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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