Genetic Variant NM_001371072.1:c.184G>T (chrX-47239077-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371072.1(USP11):c.184G>T(p.Val62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,279 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

USP11
NM_001371072.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

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]

USP11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16643181).

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.184G>T	p.Val62Leu	missense	Exon 2 of 21	NP_001358001.1	G5E9A6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP11	ENST00000377107.7	TSL:1 MANE Select	c.184G>T	p.Val62Leu	missense	Exon 2 of 21	ENSP00000366311.2	G5E9A6
USP11	ENST00000218348.7	TSL:1	c.313G>T	p.Val105Leu	missense	Exon 2 of 21	ENSP00000218348.3	P51784
USP11	ENST00000469080.5	TSL:1	n.237G>T		non_coding_transcript_exon	Exon 2 of 19

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000115

AC:

AN:

174191

AF XY:

0.0000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000745

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:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1095279

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360917

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.0000571

AC:

AN:

35006

Ashkenazi Jewish (ASJ)

AF:

0.0000518

AC:

AN:

19319

East Asian (EAS)

AF:

0.00

AC:

AN:

30149

South Asian (SAS)

AF:

0.00

AC:

AN:

53506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40299

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840522

Other (OTH)

AF:

0.00

AC:

AN:

45981

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.73

M_CAP

Benign

0.062

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

1.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.2

REVEL

Benign

0.074

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.015

Vest4

0.14

MutPred

0.51

Gain of sheet (P = 0.0477)

MVP

0.72

MPC

0.71

ClinPred

0.19

GERP RS

5.0

Varity_R

0.49

gMVP

0.83

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over