rs758704238

chrX-41183983-C-CT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001039591.3(USP9X):c.3149-8dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 1,192,392 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,131 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., 159 hem., cov: 22)
  • Exomes 𝑓: 0.0087 (36 hom. 2972 hem.)
• Consequence: USP9X NM_001039591.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.165

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 -12 ACMG points.

• BP6: Variant X-41183983-C-CT is Benign according to our data. Variant chrX-41183983-C-CT is described in ClinVar as [Benign]. Clinvar id is 445459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd at 159 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP9X	NM_001039591.3	c.3149-8dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378308.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9X	ENST00000378308.7	c.3149-8dup		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001039591.3	P4

Frequencies

GnomAD3 genomes AF: 0.00585 AC: 652 AN: 111426 Hom.: 1 Cov.: 22 AF XY: 0.00473 AC XY: 159 AN XY: 33622

Gnomad AFR AF: 0.00131

Gnomad AMI AF: 0.00147

Gnomad AMR AF: 0.00181

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00623

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00331

GnomAD3 exomes AF: 0.00586 AC: 941 AN: 160631 Hom.: 4 AF XY: 0.00571 AC XY: 297 AN XY: 51969

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00342

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00695

Gnomad NFE exome AF: 0.00976

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00868 AC: 9377 AN: 1080913 Hom.: 36 Cov.: 29 AF XY: 0.00847 AC XY: 2972 AN XY: 350919

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.00750

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00585 AC: 652 AN: 111479 Hom.: 1 Cov.: 22 AF XY: 0.00472 AC XY: 159 AN XY: 33685

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00181

Gnomad4 ASJ AF: 0.00492

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00112

Gnomad4 FIN AF: 0.00623

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00327

Alfa AF: 0.00716 Hom.: 46

Bravo AF: 0.00513

Asia WGS AF: 0.000399 AC: 1 AN: 2519

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

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: rs758704238; hg19: chrX-41043236;