Genetic Variant USP51:p.Leu708Val (chrX-55486818-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_201286.4(USP51):c.2122C>G(p.Leu708Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,191,748 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 3 hem. )

Consequence

USP51
NM_201286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Publications

0 publications found

Variant links:

Genes affected

USP51 (HGNC:23086): (ubiquitin specific peptidase 51) Enables chromatin binding activity; histone binding activity; and thiol-dependent deubiquitinase. Involved in histone deubiquitination; regulation of cell cycle process; and regulation of double-strand break repair. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

USP51 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058706045).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201286.4. 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
	USP51	NM_201286.4	MANE Select	c.2122C>G	p.Leu708Val	missense	Exon 3 of 3	NP_958443.1	Q70EK9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP51	ENST00000500968.4	TSL:1 MANE Select	c.2122C>G	p.Leu708Val	missense	Exon 3 of 3	ENSP00000423333.2	Q70EK9
USP51	ENST00000586165.1	TSL:1	c.1276C>G	p.Leu426Val	missense	Exon 2 of 2	ENSP00000490435.1	A0A1B0GVA6
USP51	ENST00000933765.1		c.2122C>G	p.Leu708Val	missense	Exon 2 of 2	ENSP00000603824.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111665

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00114

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:

0.0000363

AC:

AN:

165197

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00104

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:

0.0000148

AC:

AN:

1080083

Hom.:

Cov.:

AF XY:

0.00000856

AC XY:

AN XY:

350629

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25802

American (AMR)

AF:

0.00

AC:

AN:

33133

Ashkenazi Jewish (ASJ)

AF:

0.000657

AC:

AN:

18260

East Asian (EAS)

AF:

0.00

AC:

AN:

30007

South Asian (SAS)

AF:

0.00

AC:

AN:

50640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

832843

Other (OTH)

AF:

0.0000221

AC:

AN:

45296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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

AF:

0.0000269

AC:

AN:

111665

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33861

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30632

American (AMR)

AF:

0.00

AC:

AN:

10621

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3580

South Asian (SAS)

AF:

0.00

AC:

AN:

2651

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6019

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53101

Other (OTH)

AF:

0.00

AC:

AN:

1500

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

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:

0.000130

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.41

M_CAP

Benign

0.011

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

REVEL

Benign

0.051

Sift

Benign

0.036

Sift4G

Uncertain

0.056

Polyphen

0.49

Vest4

0.048

MutPred

0.22

Gain of ubiquitination at K705 (P = 0.0972)

MVP

0.11

MPC

0.64

ClinPred

0.14

GERP RS

-0.34

Varity_R

0.13

gMVP

0.63

Mutation Taster

=92/8

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

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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