rs55900117

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039591.3(USP9X):c.4603+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,128,223 control chromosomes in the GnomAD database, including 67 homozygotes. There are 4,105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 6 hom., 224 hem., cov: 24)

Exomes 𝑓: 0.013 ( 61 hom. 3881 hem. )

Consequence

USP9X
NM_001039591.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.234

Publications

1 publications found

Variant links:

COSMIC-nc: COSV61069618

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-restricted
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, X-linked 99
Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

USP9X links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-41198769-A-G is Benign according to our data. Variant chrX-41198769-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00762 (862/113154) while in subpopulation NFE AF = 0.0134 (717/53420). AF 95% confidence interval is 0.0126. There are 6 homozygotes in GnomAd4. There are 224 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9X	NM_001039591.3 link	c.4603+19A>G		intron_variant	Intron 30 of 44	ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7 link	c.4603+19A>G		intron_variant	Intron 30 of 44	5	NM_001039591.3	ENSP00000367558.2

Frequencies

GnomAD3 genomes

AF:

0.00764

AC:

864

AN:

113099

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00290

Gnomad AMR

AF:

0.00346

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00423

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00742

AC:

1044

AN:

140636

AF XY:

0.00744

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00340

Gnomad ASJ exome

AF:

0.00175

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.00672

GnomAD4 exome

AF:

0.0129

AC:

13105

AN:

1015069

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

3881

AN XY:

294365

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

24439

American (AMR)

AF:

0.00327

AC:

104

AN:

31767

Ashkenazi Jewish (ASJ)

AF:

0.00208

AC:

AN:

18284

East Asian (EAS)

AF:

0.00

AC:

AN:

28771

South Asian (SAS)

AF:

0.00460

AC:

223

AN:

48447

European-Finnish (FIN)

AF:

0.00200

AC:

AN:

38980

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

3562

European-Non Finnish (NFE)

AF:

0.0157

AC:

12174

AN:

777666

Other (OTH)

AF:

0.0100

AC:

432

AN:

43153

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

460

920

1379

1839

2299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

466

932

1398

1864

2330

<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

AF:

0.00762

AC:

862

AN:

113154

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

224

AN XY:

35302

show subpopulations

African (AFR)

AF:

0.00211

AC:

AN:

31245

American (AMR)

AF:

0.00345

AC:

AN:

10721

Ashkenazi Jewish (ASJ)

AF:

0.00263

AC:

AN:

2664

East Asian (EAS)

AF:

0.00

AC:

AN:

3634

South Asian (SAS)

AF:

0.00389

AC:

AN:

2830

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

6188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0134

AC:

717

AN:

53420

Other (OTH)

AF:

0.00972

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00941

Hom.:

Bravo

AF:

0.00744

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 29, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.38

(source)

DANN

Benign

0.71

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over