dbSNP rs10463: USP9X:c.*164A>G (chrX-41232688-A-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001039591.3(USP9X):c.*164A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0816 in 636,648 control chromosomes in the GnomAD database, including 1,707 homozygotes. There are 13,354 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 216 hom., 1898 hem., cov: 23)

Exomes 𝑓: 0.086 ( 1491 hom. 11456 hem. )

Consequence

USP9X
NM_001039591.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.34

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 was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant X-41232688-A-G is Benign according to our data. Variant chrX-41232688-A-G is described in ClinVar as [Benign]. Clinvar id is 1296676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9X	NM_001039591.3 link	c.*164A>G		3_prime_UTR_variant	Exon 45 of 45	ENST00000378308.7	NP_001034680.2	Q93008-1Q86X58Q6P468

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7 link	c.*164A>G		3_prime_UTR_variant	Exon 45 of 45	5	NM_001039591.3	ENSP00000367558.2		Q93008-1

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

6755

AN:

111941

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000550

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.0561

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.0539

GnomAD4 exome

AF:

0.0862

AC:

45220

AN:

524658

Hom.:

1491

Cov.:

AF XY:

0.0992

AC XY:

11456

AN XY:

115458

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

AC:

168

AN:

13301

Gnomad4 AMR exome

AF:

0.0382

AC:

538

AN:

14099

Gnomad4 ASJ exome

AF:

0.113

AC:

1174

AN:

10385

Gnomad4 EAS exome

AF:

0.000129

AC:

AN:

23258

Gnomad4 SAS exome

AF:

0.0696

AC:

1674

AN:

24060

Gnomad4 FIN exome

AF:

0.0644

AC:

1961

AN:

30438

Gnomad4 NFE exome

AF:

0.0982

AC:

37384

AN:

380869

Gnomad4 Remaining exome

AF:

0.0777

AC:

1990

AN:

25603

Heterozygous variant carriers

1430

2859

4289

5718

7148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1148

2296

3444

4592

5740

<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:

0.0603

AC:

6755

AN:

111990

Hom.:

216

Cov.:

AF XY:

0.0555

AC XY:

1898

AN XY:

34176

show subpopulations

Gnomad4 AFR

AF:

0.0124

AC:

0.0123533

AN:

0.0123533

Gnomad4 AMR

AF:

0.0440

AC:

0.0439821

AN:

0.0439821

Gnomad4 ASJ

AF:

0.122

AC:

0.121673

AN:

0.121673

Gnomad4 EAS

AF:

0.000552

AC:

0.000551724

AN:

0.000551724

Gnomad4 SAS

AF:

0.0439

AC:

0.0439399

AN:

0.0439399

Gnomad4 FIN

AF:

0.0561

AC:

0.0561182

AN:

0.0561182

Gnomad4 NFE

AF:

0.0925

AC:

0.0925128

AN:

0.0925128

Gnomad4 OTH

AF:

0.0526

AC:

0.0525624

AN:

0.0525624

Heterozygous variant carriers

237

474

712

949

1186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0737

Hom.:

4034

Bravo

AF:

0.0557

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

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.

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