Variant rs146661515 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001039591.3(USP9X):c.6084C>T(p.Pro2028=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,198,825 control chromosomes in the GnomAD database, including 22 homozygotes. There are 1,135 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., 131 hem., cov: 22)

Exomes 𝑓: 0.0028 ( 22 hom. 1004 hem. )

Consequence

USP9X
NM_001039591.3 splice_region, synonymous

Scores

Splicing: ADA: 0.00009426

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.51

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]

USP9X links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-41216651-C-T is Benign according to our data. Variant chrX-41216651-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-41216651-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=3.51 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 131 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9X	NM_001039591.3 linkuse as main transcript	c.6084C>T	p.Pro2028=	splice_region_variant, synonymous_variant	35/45	ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7 linkuse as main transcript	c.6084C>T	p.Pro2028=	splice_region_variant, synonymous_variant	35/45	5	NM_001039591.3	ENSP00000367558	P4	Q93008-1

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

301

AN:

111467

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

131

AN XY:

33653

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

Gnomad ASJ

AF:

0.00151

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00192

Gnomad OTH

AF:

0.00333

GnomAD3 exomes

AF:

0.00420

AC:

710

AN:

169079

Hom.:

AF XY:

0.00395

AC XY:

228

AN XY:

57775

show subpopulations

Gnomad AFR exome

AF:

0.000331

Gnomad AMR exome

AF:

0.0000762

Gnomad ASJ exome

AF:

0.00195

Gnomad EAS exome

AF:

0.0000751

Gnomad SAS exome

AF:

0.000182

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.00217

Gnomad OTH exome

AF:

0.00697

GnomAD4 exome

AF:

0.00276

AC:

2997

AN:

1087311

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

1004

AN XY:

354063

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0000999

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.00270

AC:

301

AN:

111514

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

131

AN XY:

33710

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.0000954

Gnomad4 ASJ

AF:

0.00151

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0309

Gnomad4 NFE

AF:

0.00192

Gnomad4 OTH

AF:

0.00329

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.000854

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 30, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 15, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 24, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.1

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000094

dbscSNV1_RF

Benign

0.024

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over