chrX-55486967-T-C

Variant names:

• chrX-55486967-T-C
• NM_201286.4:c.1973A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201286.4(USP51):​c.1973A>G​(p.His658Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: USP51 NM_201286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26719403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201286.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP51	NM_201286.4	MANE Select	c.1973A>G	p.His658Arg	missense	Exon 3 of 3	NP_958443.1	Q70EK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP51	ENST00000500968.4	TSL:1 MANE Select	c.1973A>G	p.His658Arg	missense	Exon 3 of 3	ENSP00000423333.2	Q70EK9
	USP51	ENST00000586165.1	TSL:1	c.1127A>G	p.His376Arg	missense	Exon 2 of 2	ENSP00000490435.1	A0A1B0GVA6
	USP51	ENST00000933765.1		c.1973A>G	p.His658Arg	missense	Exon 2 of 2	ENSP00000603824.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000273 AC: 3 AN: 1098221 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3 AN XY: 363581

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842126

Other (OTH) AF: 0.0000434 AC: 2 AN: 46097

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		7.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.16
Sift	Benign	0.48	T
Sift4G	Benign	0.53	T
Polyphen		0.024	B
Vest4		0.24
MutPred		0.73		Loss of catalytic residue at G659 (P = 0.0762)
MVP		0.21
MPC		1.8
ClinPred		0.71	D
GERP RS		3.0
Varity_R		0.33
gMVP		0.82
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-55513400;