Genetic Variant USP11:p.Pro462Pro (chrX-47242288-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001371072.1(USP11):c.1386G>A(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,210,278 control chromosomes in the GnomAD database, including 110 homozygotes. There are 1,020 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 11 hom., 95 hem., cov: 23)

Exomes 𝑓: 0.0026 ( 99 hom. 925 hem. )

Consequence

USP11
NM_001371072.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-47242288-G-A is Benign according to our data. Variant chrX-47242288-G-A is described in ClinVar as [Benign]. Clinvar id is 716704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47242288-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP11	NM_001371072.1 link	c.1386G>A	p.Pro462Pro	synonymous_variant	Exon 10 of 21	ENST00000377107.7	NP_001358001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP11	ENST00000377107.7 link	c.1386G>A	p.Pro462Pro	synonymous_variant	Exon 10 of 21	1	NM_001371072.1	ENSP00000366311.2		G5E9A6

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

325

AN:

112519

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

AN XY:

34677

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.0702

Gnomad SAS

AF:

0.00365

Gnomad FIN

AF:

0.000648

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000751

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00669

AC:

1215

AN:

181725

Hom.:

AF XY:

0.00608

AC XY:

403

AN XY:

66337

show subpopulations

Gnomad AFR exome

AF:

0.000384

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0822

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00260

AC:

2855

AN:

1097707

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

925

AN XY:

363075

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0774

Gnomad4 SAS exome

AF:

0.000999

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.0000641

Gnomad4 OTH exome

AF:

0.00764

GnomAD4 genome

AF:

0.00287

AC:

323

AN:

112571

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

AN XY:

34739

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.00280

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.0698

Gnomad4 SAS

AF:

0.00366

Gnomad4 FIN

AF:

0.000648

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00345

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.5

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over