chrX-47239455-C-T

Variant names:

• chrX-47239455-C-T
• rs756982370
• NM_001371072.1:c.391C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001371072.1(USP11):​c.391C>T​(p.His131Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,209,936 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.0000082 (0 hom. 3 hem.)
• Consequence: USP11 NM_001371072.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.712
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11615154).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371072.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP11	NM_001371072.1	MANE Select	c.391C>T	p.His131Tyr	missense	Exon 3 of 21	NP_001358001.1	G5E9A6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP11	ENST00000377107.7	TSL:1 MANE Select	c.391C>T	p.His131Tyr	missense	Exon 3 of 21	ENSP00000366311.2	G5E9A6
	USP11	ENST00000218348.7	TSL:1	c.520C>T	p.His174Tyr	missense	Exon 3 of 21	ENSP00000218348.3	P51784
	USP11	ENST00000469080.5	TSL:1	n.444C>T		non_coding_transcript_exon	Exon 3 of 19

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 112059 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000386 AC: 7 AN: 181331 AF XY: 0.0000151

Gnomad AFR exome AF: 0.000230

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.00000820 AC: 9 AN: 1097877 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 3 AN XY: 363285

African (AFR) AF: 0.000114 AC: 3 AN: 26402

American (AMR) AF: 0.000114 AC: 4 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19316

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 53980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842084

Other (OTH) AF: 0.0000434 AC: 2 AN: 46084

GnomAD4 genome AF: 0.000125 AC: 14 AN: 112059 Hom.: 0 Cov.: 23 AF XY: 0.0000584 AC XY: 2 AN XY: 34221

African (AFR) AF: 0.000390 AC: 12 AN: 30793

American (AMR) AF: 0.000188 AC: 2 AN: 10638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2715

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6081

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53166

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000117

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.71
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.022	D
Polyphen		0.86	P
Vest4		0.30
MVP		0.31
MPC		1.5
ClinPred		0.064	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.36
gMVP		0.52
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs756982370; hg19: chrX-47098854;