X-55488621-G-C

Variant names:

• chrX-55488621-G-C
• NM_201286.4:c.319C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201286.4(USP51):​c.319C>G​(p.Arg107Gly) 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. 14/21 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: 0.0000038 (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: 2.44
• 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]

ENSG00000288739 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23293537).

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.319C>G	p.Arg107Gly	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.319C>G	p.Arg107Gly	missense	Exon 3 of 3	ENSP00000423333.2	Q70EK9
	USP51	ENST00000586165.1	TSL:1	c.123+73C>G		intron	N/A	ENSP00000490435.1	A0A1B0GVA6
	USP51	ENST00000933765.1		c.319C>G	p.Arg107Gly	missense	Exon 2 of 2	ENSP00000603824.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000384 AC: 4 AN: 1040900 Hom.: 0 Cov.: 31 AF XY: 0.00000901 AC XY: 3 AN XY: 332780

African (AFR) AF: 0.0000401 AC: 1 AN: 24944

American (AMR) AF: 0.00 AC: 0 AN: 30228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17784

East Asian (EAS) AF: 0.00 AC: 0 AN: 27282

South Asian (SAS) AF: 0.00 AC: 0 AN: 48553

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3174

European-Non Finnish (NFE) AF: 0.00000367 AC: 3 AN: 817997

Other (OTH) AF: 0.00 AC: 0 AN: 43976

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	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.088
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.35	T
Polyphen		0.98	D
Vest4		0.30
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.068
MPC		0.81
ClinPred		0.43	T
GERP RS		0.34
PromoterAI		0.026	Neutral
Varity_R		0.24
gMVP		0.22
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chrX-55515054;