rs5963931

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039591.3(USP9X):​c.4825-372A>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_001039591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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.

• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9X	NM_001039591.3	c.4825-372A>G		intron_variant		ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7	c.4825-372A>G		intron_variant		5	NM_001039591.3	ENSP00000367558	P4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 45892 AN: 110718 Hom.: 7024 Cov.: 23 AF XY: 0.410 AC XY: 13514 AN XY: 32986

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

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.462

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.447

Alfa AF: 0.414 Hom.: 8949

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.51

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: rs5963931; hg19: chrX-41064184;