Variant chrX-55488659-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_201286.4(USP51):c.281G>C(p.Ser94Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,077,683 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

USP51
NM_201286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.331

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06733537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USP51	NM_201286.4 linkuse as main transcript	c.281G>C	p.Ser94Thr	missense_variant	3/3	ENST00000500968.4
USP51	XM_017029300.2 linkuse as main transcript	c.281G>C	p.Ser94Thr	missense_variant	3/3
USP51	XM_017029301.2 linkuse as main transcript	c.281G>C	p.Ser94Thr	missense_variant	2/2
USP51	XM_047441870.1 linkuse as main transcript	c.281G>C	p.Ser94Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP51	ENST00000500968.4 linkuse as main transcript	c.281G>C	p.Ser94Thr	missense_variant	3/3	1	NM_201286.4	P1
USP51	ENST00000586165.1 linkuse as main transcript	c.124+35G>C		intron_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000136

AC:

AN:

146775

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

45221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000391

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:

0.0000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1077683

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

352743

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.281G>C (p.S94T) alteration is located in exon 2 (coding exon 1) of the USP51 gene. This alteration results from a G to C substitution at nucleotide position 281, causing the serine (S) at amino acid position 94 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.37

M_CAP

Benign

0.015

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.21

REVEL

Benign

0.032

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.12

MutPred

0.15

Loss of sheet (P = 0.0817);

MVP

0.043

MPC

0.57

ClinPred

0.060

GERP RS

1.7

Varity_R

0.24

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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