X-55487767-G-T

Variant names:

• chrX-55487767-G-T
• NM_201286.4:c.1173C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201286.4(USP51):​c.1173C>A​(p.Phe391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: USP51 NM_201286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4111188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP51	NM_201286.4	c.1173C>A	p.Phe391Leu	missense_variant	Exon 3 of 3	ENST00000500968.4	NP_958443.1
USP51	XM_017029300.2	c.1173C>A	p.Phe391Leu	missense_variant	Exon 3 of 3		XP_016884789.1
USP51	XM_017029301.2	c.1173C>A	p.Phe391Leu	missense_variant	Exon 2 of 2		XP_016884790.1
USP51	XM_047441870.1	c.1173C>A	p.Phe391Leu	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	c.1173C>A	p.Phe391Leu	missense_variant	Exon 3 of 3	1	NM_201286.4	ENSP00000423333.2
USP51	ENST00000586165.1	c.327C>A	p.Phe109Leu	missense_variant	Exon 2 of 2	1		ENSP00000490435.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1173C>A (p.F391L) alteration is located in exon 2 (coding exon 1) of the USP51 gene. This alteration results from a C to A substitution at nucleotide position 1173, causing the phenylalanine (F) at amino acid position 391 to be replaced by a leucine (L). 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	0.97
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.70		Loss of catalytic residue at F391 (P = 0.0222);
MVP		0.47
MPC		1.0
ClinPred		0.99	D
GERP RS		0.35
Varity_R		0.70
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-55514200;