rs73480414

Positions:

chrX-41131500-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039591.3(USP9X):c.286G>T(p.Val96Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000811 in 1,207,655 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 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 0.00052 ( 0 hom., 14 hem., cov: 22)

Exomes 𝑓: 0.000036 ( 0 hom. 10 hem. )

Consequence

USP9X
NM_001039591.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.72

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 -19 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). The gene has 24 curated pathogenic missense variants (we use a threshold of 10). The gene has 36 curated benign missense variants. GenCC has associacion of the 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=0.051332206).

BP6

Variant X-41131500-G-T is Benign according to our data. Variant chrX-41131500-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 445500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00052 (58/111458) while in subpopulation AFR AF= 0.00182 (56/30714). AF 95% confidence interval is 0.00144. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9X	NM_001039591.3 link	c.286G>T	p.Val96Leu	missense_variant	4/45	ENST00000378308.7	NP_001034680.2	Q93008-1Q86X58Q6P468

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7 link	c.286G>T	p.Val96Leu	missense_variant	4/45	5	NM_001039591.3	ENSP00000367558.2		Q93008-1

Frequencies

GnomAD3 genomes

AF:

0.000521

AC:

AN:

111407

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

33579

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000957

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:

0.00

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.000159

AC:

AN:

182514

Hom.:

AF XY:

0.0000895

AC XY:

AN XY:

67044

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1096197

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

361729

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.0000569

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:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.000520

AC:

AN:

111458

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

33640

show subpopulations

Gnomad4 AFR

AF:

0.00182

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.0000252

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 16, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.24

Sift

Benign

0.030

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.84

P;P

Vest4

0.55

MutPred

0.31

Loss of methylation at K91 (P = 0.0918);Loss of methylation at K91 (P = 0.0918);

MVP

0.65

MPC

1.4

ClinPred

0.071

GERP RS

5.1

Varity_R

0.57

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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