X-41123388-C-T

Position:

• chrX-41123388-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039591.3(USP9X):​c.-158-83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 344,573 control chromosomes in the GnomAD database, including 2,180 homozygotes. There are 11,536 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 (893 hom., 4181 hem., cov: 22)
  • Exomes 𝑓: 0.11 (1287 hom. 7355 hem.)
• Consequence: USP9X NM_001039591.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236

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=-0.83).
• BP6: Variant X-41123388-C-T is Benign according to our data. Variant chrX-41123388-C-T is described in ClinVar as [Benign]. Clinvar id is 1289835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9X	NM_001039591.3	c.-158-83C>T		intron_variant		ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7	c.-158-83C>T		intron_variant		5	NM_001039591.3	ENSP00000367558.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 14709 AN: 111019 Hom.: 896 Cov.: 22 AF XY: 0.126 AC XY: 4180 AN XY: 33287

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0821

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0979

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.113 AC: 26419 AN: 233496 Hom.: 1287 AF XY: 0.117 AC XY: 7355 AN XY: 63132

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.0737

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0739

Gnomad4 NFE exome AF: 0.0922

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.132 AC: 14709 AN: 111077 Hom.: 893 Cov.: 22 AF XY: 0.125 AC XY: 4181 AN XY: 33355

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.121

Alfa AF: 0.115 Hom.: 727

Bravo AF: 0.152

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.62

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: rs3761593; hg19: chrX-40982641;