chrX-41219135-C-T

Variant names:

• chrX-41219135-C-T
• rs587777319
• NM_001039591.3:c.6469C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001039591.3(USP9X):​c.6469C>T​(p.Leu2157Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,208,364 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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. Synonymous variant affecting the same amino acid position (i.e. L2157L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: USP9X NM_001039591.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

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]

USP9X Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 99, syndromic, female-restricted

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, X-linked 99

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039591.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9X	NM_001039591.3	MANE Select	c.6469C>T	p.Leu2157Leu	synonymous	Exon 38 of 45	NP_001034680.2
	USP9X	NM_001410748.1		c.6484C>T	p.Leu2162Leu	synonymous	Exon 39 of 46	NP_001397677.1
	USP9X	NM_001039590.3		c.6469C>T	p.Leu2157Leu	synonymous	Exon 38 of 45	NP_001034679.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP9X	ENST00000378308.7	TSL:5 MANE Select	c.6469C>T	p.Leu2157Leu	synonymous	Exon 38 of 45	ENSP00000367558.2
	USP9X	ENST00000703987.1		c.6484C>T	p.Leu2162Leu	synonymous	Exon 38 of 45	ENSP00000515604.1
	USP9X	ENST00000324545.9	TSL:5	c.6469C>T	p.Leu2157Leu	synonymous	Exon 38 of 45	ENSP00000316357.6

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 112028 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000367

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096282 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1 AN XY: 361810

African (AFR) AF: 0.00 AC: 0 AN: 26344

American (AMR) AF: 0.00 AC: 0 AN: 35017

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19327

East Asian (EAS) AF: 0.00 AC: 0 AN: 30103

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4097

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841096

Other (OTH) AF: 0.00 AC: 0 AN: 46004

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112082 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34274

African (AFR) AF: 0.00 AC: 0 AN: 30939

American (AMR) AF: 0.00 AC: 0 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3587

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6013

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53228

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.0000359 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	6.2
DANN	Benign	0.71
PhyloP100		1.9

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

Other links and lift over

dbSNP: rs587777319; hg19: chrX-41078388;