X-47241373-A-G

Variant names:

• chrX-47241373-A-G
• rs867182050
• NM_001371072.1:c.943A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371072.1(USP11):​c.943A>G​(p.Ile315Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: USP11 NM_001371072.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04

Genes affected

USP11 (HGNC:12609): (ubiquitin specific peptidase 11) Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23 [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25734255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP11	NM_001371072.1	c.943A>G	p.Ile315Val	missense_variant	Exon 8 of 21	ENST00000377107.7	NP_001358001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP11	ENST00000377107.7	c.943A>G	p.Ile315Val	missense_variant	Exon 8 of 21	1	NM_001371072.1	ENSP00000366311.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1072A>G (p.I358V) alteration is located in exon 8 (coding exon 8) of the USP11 gene. This alteration results from a A to G substitution at nucleotide position 1072, causing the isoleucine (I) at amino acid position 358 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.083
Sift	Benign	0.050	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.067	.;B;.
Vest4		0.28
MutPred		0.53		.;Gain of phosphorylation at Y362 (P = 0.0865);.;
MVP		0.55
MPC		0.82
ClinPred		0.75	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.41

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: rs867182050; hg19: chrX-47100772;