rs5963931

Variant names:

• chrX-41204931-A-G
• rs5963931
• NM_001039591.3:c.4825-372A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-41204931-A-G
• chrX-41204931-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001410748.1(USP9X):​c.4840-372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 119,703 control chromosomes in the GnomAD database, including 7,899 homozygotes. There are 14,428 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (7029 hom., 13538 hem., cov: 23)
  • Exomes 𝑓: 0.48 (870 hom. 890 hem.)
• Consequence: USP9X NM_001410748.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410748.1. 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.4825-372A>G		intron	N/A	NP_001034680.2
	USP9X	NM_001410748.1		c.4840-372A>G		intron	N/A	NP_001397677.1
	USP9X	NM_001039590.3		c.4825-372A>G		intron	N/A	NP_001034679.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9X	ENST00000378308.7	TSL:5 MANE Select	c.4825-372A>G		intron	N/A	ENSP00000367558.2
	USP9X	ENST00000703987.1		c.4840-372A>G		intron	N/A	ENSP00000515604.1
	USP9X	ENST00000324545.9	TSL:5	c.4825-372A>G		intron	N/A	ENSP00000316357.6

Frequencies

GnomAD3 genomes AF: 0.414 AC: 45892 AN: 110718 Hom.: 7024 Cov.: 23

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.485 AC: 4332 AN: 8934 Hom.: 870 AF XY: 0.522 AC XY: 890 AN XY: 1706

African (AFR) AF: 0.292 AC: 108 AN: 370

American (AMR) AF: 0.357 AC: 121 AN: 339

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 211 AN: 342

East Asian (EAS) AF: 0.467 AC: 177 AN: 379

South Asian (SAS) AF: 0.548 AC: 85 AN: 155

European-Finnish (FIN) AF: 0.497 AC: 166 AN: 334

Middle Eastern (MID) AF: 0.682 AC: 15 AN: 22

European-Non Finnish (NFE) AF: 0.496 AC: 3151 AN: 6348

Other (OTH) AF: 0.462 AC: 298 AN: 645

GnomAD4 genome AF: 0.415 AC: 45921 AN: 110769 Hom.: 7029 Cov.: 23 AF XY: 0.410 AC XY: 13538 AN XY: 33047

African (AFR) AF: 0.294 AC: 8973 AN: 30542

American (AMR) AF: 0.372 AC: 3865 AN: 10402

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 1559 AN: 2635

East Asian (EAS) AF: 0.514 AC: 1801 AN: 3505

South Asian (SAS) AF: 0.486 AC: 1300 AN: 2676

European-Finnish (FIN) AF: 0.452 AC: 2641 AN: 5840

Middle Eastern (MID) AF: 0.467 AC: 99 AN: 212

European-Non Finnish (NFE) AF: 0.468 AC: 24699 AN: 52775

Other (OTH) AF: 0.447 AC: 677 AN: 1513

Alfa AF: 0.415 Hom.: 13743

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.51
PhyloP100		1.6
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: rs5963931; hg19: chrX-41064184;