NM_001039591.3:c.-158-329G>A

Variant names:

• chrX-41123142-G-A
• rs111451767
• NM_001039591.3:c.-158-329G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039591.3(USP9X):​c.-158-329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 111,259 control chromosomes in the GnomAD database, including 900 homozygotes. There are 4,247 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 (900 hom., 4247 hem., cov: 22)
• Consequence: USP9X NM_001039591.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-41123142-G-A is Benign according to our data. Variant chrX-41123142-G-A is described in ClinVar as [Benign]. Clinvar id is 1230956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP9X	NM_001039591.3	c.-158-329G>A		intron_variant	Intron 1 of 44	ENST00000378308.7	NP_001034680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP9X	ENST00000378308.7	c.-158-329G>A		intron_variant	Intron 1 of 44	5	NM_001039591.3	ENSP00000367558.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 14820 AN: 111207 Hom.: 903 Cov.: 22 AF XY: 0.127 AC XY: 4245 AN XY: 33421

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0806

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0936

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.133 AC: 14821 AN: 111259 Hom.: 900 Cov.: 22 AF XY: 0.127 AC XY: 4247 AN XY: 33483

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.124

Alfa AF: 0.113 Hom.: 625

Bravo AF: 0.152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.37

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: rs111451767; hg19: chrX-40982395;