Genetic Variant USP51:p.Asp296Gly (chrX-55488053-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_201286.4(USP51):c.887A>G(p.Asp296Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,210,194 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000050 ( 0 hom. 16 hem. )

Consequence

USP51
NM_201286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23160324).

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP51	NM_201286.4 link	c.887A>G	p.Asp296Gly	missense_variant	Exon 3 of 3	ENST00000500968.4	NP_958443.1	Q70EK9
USP51	XM_017029300.2 link	c.887A>G	p.Asp296Gly	missense_variant	Exon 3 of 3		XP_016884789.1	Q70EK9
USP51	XM_017029301.2 link	c.887A>G	p.Asp296Gly	missense_variant	Exon 2 of 2		XP_016884790.1	Q70EK9
USP51	XM_047441870.1 link	c.887A>G	p.Asp296Gly	missense_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.887A>G	p.Asp296Gly	missense_variant	Exon 3 of 3	1	NM_201286.4	ENSP00000423333.2		Q70EK9
USP51	ENST00000586165.1 link	c.124-83A>G		intron_variant	Intron 1 of 1	1		ENSP00000490435.1		A0A1B0GVA6

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34488

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000939

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000657

AC:

AN:

182539

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67069

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:

0.000147

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000501

AC:

AN:

1097864

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000653

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34488

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000939

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000969

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.887A>G (p.D296G) alteration is located in exon 2 (coding exon 1) of the USP51 gene. This alteration results from a A to G substitution at nucleotide position 887, causing the aspartic acid (D) at amino acid position 296 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.22

Sift

Uncertain

0.027

Sift4G

Benign

0.078

Polyphen

0.54

Vest4

0.26

MVP

0.44

MPC

1.9

ClinPred

0.42

GERP RS

3.2

Varity_R

0.69

gMVP

0.54

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