X-41183983-CTT-CTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001039591.3(USP9X):c.3149-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 1,192,392 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,131 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 1 hom., 159 hem., cov: 22)

Exomes 𝑓: 0.0087 ( 36 hom. 2972 hem. )

Consequence

USP9X
NM_001039591.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.165

Publications

0 publications found

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 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 -16 ACMG points.

BP6

Variant X-41183983-C-CT is Benign according to our data. Variant chrX-41183983-C-CT is described in ClinVar as Benign. ClinVar VariationId is 445459.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 = 0.00585 (652/111479) while in subpopulation NFE AF = 0.0101 (533/53007). AF 95% confidence interval is 0.00935. There are 1 homozygotes in GnomAd4. There are 159 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 159 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9X	NM_001039591.3 link	c.3149-8dupT		splice_region_variant, intron_variant	Intron 21 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.3149-15_3149-14insT		intron_variant	Intron 21 of 44	5	NM_001039591.3	ENSP00000367558.2

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

652

AN:

111426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00131

Gnomad AMI

AF:

0.00147

Gnomad AMR

AF:

0.00181

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00112

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00331

GnomAD2 exomes

AF:

0.00586

AC:

941

AN:

160631

AF XY:

0.00571

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00342

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00695

Gnomad NFE exome

AF:

0.00976

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00868

AC:

9377

AN:

1080913

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

2972

AN XY:

350919

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

25548

American (AMR)

AF:

0.00101

AC:

AN:

31570

Ashkenazi Jewish (ASJ)

AF:

0.00448

AC:

AN:

18544

East Asian (EAS)

AF:

0.00

AC:

AN:

29961

South Asian (SAS)

AF:

0.00183

AC:

AN:

50741

European-Finnish (FIN)

AF:

0.00750

AC:

295

AN:

39355

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.0102

AC:

8539

AN:

835781

Other (OTH)

AF:

0.00668

AC:

303

AN:

45353

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

316

632

948

1264

1580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.00585

AC:

652

AN:

111479

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

159

AN XY:

33685

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

30697

American (AMR)

AF:

0.00181

AC:

AN:

10505

Ashkenazi Jewish (ASJ)

AF:

0.00492

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00112

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.00623

AC:

AN:

5938

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0101

AC:

533

AN:

53007

Other (OTH)

AF:

0.00327

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00716

Hom.:

Bravo

AF:

0.00513

Asia WGS

AF:

0.000399

AC:

AN:

2519

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 18, 2017

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.17

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