Genetic Variant USP51:p.Asp551Asp (chrX-55487287-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_201286.4(USP51):c.1653C>T(p.Asp551Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.000423 in 1,209,635 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 181 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 0.00021 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00044 ( 0 hom. 174 hem. )

Consequence

USP51
NM_201286.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.00

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant X-55487287-G-A is Benign according to our data. Variant chrX-55487287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660697.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP51	NM_201286.4 link	c.1653C>T	p.Asp551Asp	synonymous_variant	Exon 3 of 3	ENST00000500968.4	NP_958443.1	Q70EK9
USP51	XM_017029300.2 link	c.1653C>T	p.Asp551Asp	synonymous_variant	Exon 3 of 3		XP_016884789.1	Q70EK9
USP51	XM_017029301.2 link	c.1653C>T	p.Asp551Asp	synonymous_variant	Exon 2 of 2		XP_016884790.1	Q70EK9
USP51	XM_047441870.1 link	c.1653C>T	p.Asp551Asp	synonymous_variant	Exon 2 of 2		XP_047297826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP51	ENST00000500968.4 link	c.1653C>T	p.Asp551Asp	synonymous_variant	Exon 3 of 3	1	NM_201286.4	ENSP00000423333.2		Q70EK9
USP51	ENST00000586165.1 link	c.807C>T	p.Asp269Asp	synonymous_variant	Exon 2 of 2	1		ENSP00000490435.1		A0A1B0GVA6

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

111847

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34007

show subpopulations

Gnomad AFR

AF:

0.0000651

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:

0.000414

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000258

AC:

AN:

181981

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

66525

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000580

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000445

AC:

488

AN:

1097788

Hom.:

Cov.:

AF XY:

0.000479

AC XY:

174

AN XY:

363156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000987

Gnomad4 NFE exome

AF:

0.000537

Gnomad4 OTH exome

AF:

0.000673

GnomAD4 genome

AF:

0.000215

AC:

AN:

111847

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34007

show subpopulations

Gnomad4 AFR

AF:

0.0000651

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000414

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.000249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USP51: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.3

DANN

Benign

0.44

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