X-41123645-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2 BP4

The NM_001039591.3(USP9X):c.17G>A(p.Arg6His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,097,724 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 4 hem.)
• Consequence: USP9X NM_001039591.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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 Uncertain_significance. Variant got 0 ACMG points.

• PP2: Missense variant where missense usually causes diseases, USP9X
• BP4: Computational evidence support a benign effect (MetaRNN=0.36808503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP9X	NM_001039591.3	c.17G>A	p.Arg6His	missense_variant	2/45	ENST00000378308.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP9X	ENST00000378308.7	c.17G>A	p.Arg6His	missense_variant	2/45	5	NM_001039591.3	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000555 AC: 1 AN: 180121 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66019

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097724 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4 AN XY: 363100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Dec 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	25
Dann	Uncertain	1.0
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.26
Sift	Benign	0.054	T;T
Sift4G	Benign	0.087	T;T
Polyphen		0.056	B;B
Vest4		0.60
MVP		0.68
MPC		0.92
ClinPred		0.60	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.42
gMVP		0.32

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: rs1419353367; hg19: chrX-40982898;