rs878853105

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_001039591.3(USP9X):ā€‹c.640C>Gā€‹(p.Pro214Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,208,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes š‘“: 0.000013 ( 0 hom. 3 hem. )

Consequence

USP9X
NM_001039591.3 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), USP9X. . Gene score misZ 6.4105 (greater than the threshold 3.09). GenCC has associacion of gene with non-syndromic X-linked intellectual disability, X-linked syndromic intellectual disability, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked 99, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability.
BP4
Computational evidence support a benign effect (MetaRNN=0.37151378).
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
USP9XNM_001039591.3 linkuse as main transcriptc.640C>G p.Pro214Ala missense_variant 6/45 ENST00000378308.7 NP_001034680.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USP9XENST00000378308.7 linkuse as main transcriptc.640C>G p.Pro214Ala missense_variant 6/455 NM_001039591.3 ENSP00000367558 P4Q93008-1

Frequencies

GnomAD3 genomes
AF:
0.00000892
AC:
1
AN:
112101
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34251
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1096508
Hom.:
0
Cov.:
29
AF XY:
0.00000829
AC XY:
3
AN XY:
361910
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.00000892
AC:
1
AN:
112101
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34251
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:2
Uncertain significance, criteria provided, single submitterclinical testingClinical Genetics Laboratory, Skane University Hospital LundMay 27, 2022- -
Uncertain significance, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsApr 12, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Benign
0.96
DEOGEN2
Benign
0.33
.;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.37
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.81
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.23
Sift
Benign
0.32
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.016
B;B
Vest4
0.58
MutPred
0.17
Loss of glycosylation at P214 (P = 0.0404);Loss of glycosylation at P214 (P = 0.0404);
MVP
0.42
MPC
0.79
ClinPred
0.69
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.58

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.

Other links and lift over

dbSNP: rs878853105; hg19: chrX-40996261; API