chrX-41123142-G-A

Variant names:

• chrX-41123142-G-A
• rs111451767
• NM_001039591.3:c.-158-329G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039591.3(USP9X):​c.-158-329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 111,259 control chromosomes in the GnomAD database, including 900 homozygotes. There are 4,247 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 (900 hom., 4247 hem., cov: 22)
• Consequence: USP9X NM_001039591.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-41123142-G-A is Benign according to our data. Variant chrX-41123142-G-A is described in ClinVar as Benign. ClinVar VariationId is 1230956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 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.-158-329G>A		intron	N/A	NP_001034680.2	Q93008-1
	USP9X	NM_001410748.1		c.-158-329G>A		intron	N/A	NP_001397677.1	A0A994J4R6
	USP9X	NM_001039590.3		c.-158-329G>A		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.-158-329G>A		intron	N/A	ENSP00000367558.2	Q93008-1
	USP9X	ENST00000703987.1		c.-158-329G>A		intron	N/A	ENSP00000515604.1	A0A994J4R6
	USP9X	ENST00000324545.9	TSL:5	c.-158-329G>A		intron	N/A	ENSP00000316357.6	Q93008-3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 14820 AN: 111207 Hom.: 903 Cov.: 22

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0806

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0936

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.133 AC: 14821 AN: 111259 Hom.: 900 Cov.: 22 AF XY: 0.127 AC XY: 4247 AN XY: 33483

African (AFR) AF: 0.189 AC: 5784 AN: 30589

American (AMR) AF: 0.208 AC: 2181 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 187 AN: 2638

East Asian (EAS) AF: 0.216 AC: 760 AN: 3518

South Asian (SAS) AF: 0.154 AC: 408 AN: 2644

European-Finnish (FIN) AF: 0.0587 AC: 352 AN: 5992

Middle Eastern (MID) AF: 0.0930 AC: 20 AN: 215

European-Non Finnish (NFE) AF: 0.0922 AC: 4885 AN: 52986

Other (OTH) AF: 0.124 AC: 189 AN: 1519

Alfa AF: 0.113 Hom.: 625

Bravo AF: 0.152

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.37
PhyloP100		-1.8
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: rs111451767; hg19: chrX-40982395;