X-41123388-C-T

Variant names:

• chrX-41123388-C-T
• rs3761593
• NM_001039591.3:c.-158-83C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039591.3(USP9X):​c.-158-83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 344,573 control chromosomes in the GnomAD database, including 2,180 homozygotes. There are 11,536 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (893 hom., 4181 hem., cov: 22)
  • Exomes 𝑓: 0.11 (1287 hom. 7355 hem.)
• Consequence: USP9X NM_001039591.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236
• Publications: 0 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-41123388-C-T is Benign according to our data. Variant chrX-41123388-C-T is described in ClinVar as Benign. ClinVar VariationId is 1289835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039591.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9X	NM_001039591.3	MANE Select	c.-158-83C>T		intron	N/A	NP_001034680.2	Q93008-1
	USP9X	NM_001410748.1		c.-158-83C>T		intron	N/A	NP_001397677.1	A0A994J4R6
	USP9X	NM_001039590.3		c.-158-83C>T		intron	N/A	NP_001034679.2	Q93008-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9X	ENST00000378308.7	TSL:5 MANE Select	c.-158-83C>T		intron	N/A	ENSP00000367558.2	Q93008-1
	USP9X	ENST00000703987.1		c.-158-83C>T		intron	N/A	ENSP00000515604.1	A0A994J4R6
	USP9X	ENST00000324545.9	TSL:5	c.-158-83C>T		intron	N/A	ENSP00000316357.6	Q93008-3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 14709 AN: 111019 Hom.: 896 Cov.: 22

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0821

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0979

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.113 AC: 26419 AN: 233496 Hom.: 1287 AF XY: 0.117 AC XY: 7355 AN XY: 63132

African (AFR) AF: 0.187 AC: 1258 AN: 6733

American (AMR) AF: 0.247 AC: 2128 AN: 8612

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 533 AN: 7230

East Asian (EAS) AF: 0.229 AC: 3348 AN: 14590

South Asian (SAS) AF: 0.140 AC: 2912 AN: 20803

European-Finnish (FIN) AF: 0.0739 AC: 1118 AN: 15132

Middle Eastern (MID) AF: 0.0734 AC: 73 AN: 995

European-Non Finnish (NFE) AF: 0.0922 AC: 13379 AN: 145180

Other (OTH) AF: 0.117 AC: 1670 AN: 14221

GnomAD4 genome AF: 0.132 AC: 14709 AN: 111077 Hom.: 893 Cov.: 22 AF XY: 0.125 AC XY: 4181 AN XY: 33355

African (AFR) AF: 0.187 AC: 5700 AN: 30485

American (AMR) AF: 0.208 AC: 2182 AN: 10486

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 178 AN: 2630

East Asian (EAS) AF: 0.213 AC: 745 AN: 3499

South Asian (SAS) AF: 0.152 AC: 405 AN: 2669

European-Finnish (FIN) AF: 0.0611 AC: 361 AN: 5912

Middle Eastern (MID) AF: 0.0977 AC: 21 AN: 215

European-Non Finnish (NFE) AF: 0.0920 AC: 4875 AN: 52965

Other (OTH) AF: 0.121 AC: 186 AN: 1534

Alfa AF: 0.115 Hom.: 727

Bravo AF: 0.152

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-0.24
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

Other links and lift over

dbSNP: rs3761593; hg19: chrX-40982641;