Genetic Variant USP11:p.Val4Val (chrX-47233055-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001371072.1(USP11):c.12C>T(p.Val4Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,208,692 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 4 hem. )

Consequence

USP11
NM_001371072.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0980

Publications

1 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant X-47233055-C-T is Benign according to our data. Variant chrX-47233055-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660417.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.098 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 4 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.12C>T	p.Val4Val	synonymous	Exon 1 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.12C>T	p.Val4Val	synonymous	Exon 1 of 21	ENSP00000366311.2	G5E9A6
USP11	ENST00000218348.7	TSL:1	c.141C>T	p.Val47Val	synonymous	Exon 1 of 21	ENSP00000218348.3	P51784
USP11	ENST00000469080.5	TSL:1	n.26C>T		non_coding_transcript_exon	Exon 1 of 19

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000288

AC:

AN:

173648

AF XY:

0.0000489

show subpopulations

Gnomad AFR exome

AF:

0.0000821

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000744

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1096328

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361862

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26376

American (AMR)

AF:

0.000114

AC:

AN:

35008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19344

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30163

South Asian (SAS)

AF:

0.00

AC:

AN:

53891

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841159

Other (OTH)

AF:

0.00

AC:

AN:

45995

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000445

AC:

AN:

112364

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34520

show subpopulations

African (AFR)

AF:

0.000162

AC:

AN:

30874

American (AMR)

AF:

0.00

AC:

AN:

10662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3592

South Asian (SAS)

AF:

0.00

AC:

AN:

2763

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6139

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53255

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

8.1

(source)

DANN

Benign

0.87

PhyloP100

0.098

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over