X-55486967-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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

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=0.26719403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP51	NM_201286.4	c.1973A>G	p.His658Arg	missense_variant	Exon 3 of 3	ENST00000500968.4	NP_958443.1
USP51	XM_017029300.2	c.1973A>G	p.His658Arg	missense_variant	Exon 3 of 3		XP_016884789.1
USP51	XM_017029301.2	c.1973A>G	p.His658Arg	missense_variant	Exon 2 of 2		XP_016884790.1
USP51	XM_047441870.1	c.1973A>G	p.His658Arg	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.1973A>G	p.His658Arg	missense_variant	Exon 3 of 3	1	NM_201286.4	ENSP00000423333.2
USP51	ENST00000586165.1	c.1127A>G	p.His376Arg	missense_variant	Exon 2 of 2	1		ENSP00000490435.1

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

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1973A>G (p.H658R) 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 1973, causing the histidine (H) at amino acid position 658 to be replaced by an arginine (R). 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	0.23
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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-55513400;