X-47233024-G-A

Variant names:

• chrX-47233024-G-A
• rs149757747
• ENST00000218348.7:c.110G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000218348.7(USP11):​c.110G>A​(p.Cys37Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,210,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 249 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 0.00044 (0 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.00072 (0 hom. 238 hem.)
• Consequence: USP11 ENST00000218348.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036254793).
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000218348.7. 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.-20G>A		5_prime_UTR	Exon 1 of 21	NP_001358001.1	G5E9A6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP11	ENST00000218348.7	TSL:1	c.110G>A	p.Cys37Tyr	missense	Exon 1 of 21	ENSP00000218348.3	P51784
	USP11	ENST00000377107.7	TSL:1 MANE Select	c.-20G>A		5_prime_UTR	Exon 1 of 21	ENSP00000366311.2	G5E9A6
	USP11	ENST00000970028.1		c.-20G>A		5_prime_UTR	Exon 1 of 21	ENSP00000640087.1

Frequencies

GnomAD3 genomes AF: 0.000435 AC: 49 AN: 112519 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000562

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: 0.000751

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.000255 AC: 46 AN: 180508 AF XY: 0.000211

Gnomad AFR exome AF: 0.0000770

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: 0.000503

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000725 AC: 796 AN: 1098013 Hom.: 0 Cov.: 31 AF XY: 0.000655 AC XY: 238 AN XY: 363371

African (AFR) AF: 0.0000758 AC: 2 AN: 26398

American (AMR) AF: 0.0000569 AC: 2 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54106

European-Finnish (FIN) AF: 0.000148 AC: 6 AN: 40501

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.000912 AC: 768 AN: 842035

Other (OTH) AF: 0.000369 AC: 17 AN: 46077

GnomAD4 genome AF: 0.000435 AC: 49 AN: 112519 Hom.: 0 Cov.: 23 AF XY: 0.000317 AC XY: 11 AN XY: 34677

African (AFR) AF: 0.00 AC: 0 AN: 30941

American (AMR) AF: 0.000562 AC: 6 AN: 10667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3595

South Asian (SAS) AF: 0.00 AC: 0 AN: 2747

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6193

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

European-Non Finnish (NFE) AF: 0.000751 AC: 40 AN: 53289

Other (OTH) AF: 0.00199 AC: 3 AN: 1509

Alfa AF: 0.000629 Hom.: 28

Bravo AF: 0.000276

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00104 AC: 7

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000818

EpiControl AF: 0.000416

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	0.092
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.070
Sift	Benign	0.057	T
Sift4G	Uncertain	0.034	D
Polyphen		0.028	B
Vest4		0.17
MVP		0.26
MPC		0.98
ClinPred		0.016	T
GERP RS		4.4
PromoterAI		-0.033	Neutral
Varity_R		0.27
gMVP		0.67
Mutation Taster		=297/3	polymorphism

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: rs149757747; hg19: chrX-47092423; COSMIC: COSV52093362; COSMIC: COSV52093362;