X-41232688-A-G

Position:

• chrX-41232688-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001039591.3(USP9X):​c.*164A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0816 in 636,648 control chromosomes in the GnomAD database, including 1,707 homozygotes. There are 13,354 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (216 hom., 1898 hem., cov: 23)
  • Exomes 𝑓: 0.086 (1491 hom. 11456 hem.)
• Consequence: USP9X NM_001039591.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.34

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant X-41232688-A-G is Benign according to our data. Variant chrX-41232688-A-G is described in ClinVar as [Benign]. Clinvar id is 1296676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP9X	NM_001039591.3	c.*164A>G		3_prime_UTR_variant	45/45	ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7	c.*164A>G		3_prime_UTR_variant	45/45	5	NM_001039591.3	ENSP00000367558	P4

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 6755 AN: 111941 Hom.: 216 Cov.: 23 AF XY: 0.0556 AC XY: 1897 AN XY: 34117

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000550

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0561

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0539

GnomAD4 exome AF: 0.0862 AC: 45220 AN: 524658 Hom.: 1491 Cov.: 8 AF XY: 0.0992 AC XY: 11456 AN XY: 115458

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0382

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.0696

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.0982

Gnomad4 OTH exome AF: 0.0777

GnomAD4 genome AF: 0.0603 AC: 6755 AN: 111990 Hom.: 216 Cov.: 23 AF XY: 0.0555 AC XY: 1898 AN XY: 34176

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.000552

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0561

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0799 Hom.: 2981

Bravo AF: 0.0557

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	Sep 04, 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	-0.36
CADD	Benign	12
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10463; hg19: chrX-41091941;