X-55487628-G-A

Variant summary

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

The NM_201286.4(USP51):​c.1312C>T​(p.His438Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,210,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

USP51
NM_201286.4 missense

Scores

4
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25
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]

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=0.22583356).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP51NM_201286.4 linkc.1312C>T p.His438Tyr missense_variant Exon 3 of 3 ENST00000500968.4 NP_958443.1 Q70EK9
USP51XM_017029300.2 linkc.1312C>T p.His438Tyr missense_variant Exon 3 of 3 XP_016884789.1 Q70EK9
USP51XM_017029301.2 linkc.1312C>T p.His438Tyr missense_variant Exon 2 of 2 XP_016884790.1 Q70EK9
USP51XM_047441870.1 linkc.1312C>T p.His438Tyr missense_variant Exon 2 of 2 XP_047297826.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP51ENST00000500968.4 linkc.1312C>T p.His438Tyr missense_variant Exon 3 of 3 1 NM_201286.4 ENSP00000423333.2 Q70EK9
USP51ENST00000586165.1 linkc.466C>T p.His156Tyr missense_variant Exon 2 of 2 1 ENSP00000490435.1 A0A1B0GVA6

Frequencies

GnomAD3 genomes
AF:
0.00000891
AC:
1
AN:
112174
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34338
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:
0.000279
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
GnomAD3 exomes
AF:
0.0000164
AC:
3
AN:
183350
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.0000525
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000364
AC:
4
AN:
1098196
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
2
AN XY:
363550
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000568
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000891
AC:
1
AN:
112228
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34402
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000280
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1312C>T (p.H438Y) alteration is located in exon 2 (coding exon 1) of the USP51 gene. This alteration results from a C to T substitution at nucleotide position 1312, causing the histidine (H) at amino acid position 438 to be replaced by a tyrosine (Y). 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
Pathogenic
0.77
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.88
L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-5.4
D
REVEL
Benign
0.25
Sift
Benign
0.079
T
Sift4G
Pathogenic
0.0010
D
Polyphen
0.97
D
Vest4
0.47
MutPred
0.64
Gain of catalytic residue at I437 (P = 0.0741);
MVP
0.36
MPC
1.7
ClinPred
0.65
D
GERP RS
3.0
Varity_R
0.69
gMVP
0.49

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.

Other links and lift over

dbSNP: rs769364619; hg19: chrX-55514061; API