rs55900117

chrX-41198769-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001039591.3(USP9X):c.4603+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,128,223 control chromosomes in the GnomAD database, including 67 homozygotes. There are 4,105 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 0.0076 (6 hom., 224 hem., cov: 24)
  • Exomes 𝑓: 0.013 (61 hom. 3881 hem.)
• Consequence: USP9X NM_001039591.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.234

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-41198769-A-G is Benign according to our data. Variant chrX-41198769-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0129 (13105/1015069) while in subpopulation NFE AF= 0.0157 (12174/777666). AF 95% confidence interval is 0.0154. There are 61 homozygotes in gnomad4_exome. There are 3881 alleles in male gnomad4_exome subpopulation. Median coverage is 19. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP9X	NM_001039591.3	c.4603+19A>G		intron_variant		ENST00000378308.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9X	ENST00000378308.7	c.4603+19A>G		intron_variant		5	NM_001039591.3	P4

Frequencies

GnomAD3 genomes AF: 0.00764 AC: 864 AN: 113099 Hom.: 6 Cov.: 24 AF XY: 0.00639 AC XY: 225 AN XY: 35237

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00290

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.00263

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00423

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00742 AC: 1044 AN: 140636 Hom.: 4 AF XY: 0.00744 AC XY: 273 AN XY: 36718

Gnomad AFR exome AF: 0.00207

Gnomad AMR exome AF: 0.00340

Gnomad ASJ exome AF: 0.00175

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00561

Gnomad FIN exome AF: 0.00183

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00672

GnomAD4 exome AF: 0.0129 AC: 13105 AN: 1015069 Hom.: 61 Cov.: 19 AF XY: 0.0132 AC XY: 3881 AN XY: 294365

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.00208

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00460

Gnomad4 FIN exome AF: 0.00200

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.00762 AC: 862 AN: 113154 Hom.: 6 Cov.: 24 AF XY: 0.00635 AC XY: 224 AN XY: 35302

Gnomad4 AFR AF: 0.00211

Gnomad4 AMR AF: 0.00345

Gnomad4 ASJ AF: 0.00263

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00389

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.00972

Alfa AF: 0.00941 Hom.: 85

Bravo AF: 0.00744

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.38
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs55900117; hg19: chrX-41058022; COSMIC: COSV61069618; COSMIC: COSV61069618;