X-55488448-T-C

Variant names:

• chrX-55488448-T-C
• rs138173648
• NM_201286.4:c.492A>G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_201286.4(USP51):​c.492A>G​(p.Arg164Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,208,784 control chromosomes in the GnomAD database, including 4 homozygotes. There are 929 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., 50 hem., cov: 23)
  • Exomes 𝑓: 0.0024 (2 hom. 879 hem.)
• Consequence: USP51 NM_201286.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.345

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-55488448-T-C is Benign according to our data. Variant chrX-55488448-T-C is described in ClinVar as [Benign]. Clinvar id is 775459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.345 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP51	NM_201286.4	c.492A>G	p.Arg164Arg	synonymous_variant	Exon 3 of 3	ENST00000500968.4	NP_958443.1
USP51	XM_017029300.2	c.492A>G	p.Arg164Arg	synonymous_variant	Exon 3 of 3		XP_016884789.1
USP51	XM_017029301.2	c.492A>G	p.Arg164Arg	synonymous_variant	Exon 2 of 2		XP_016884790.1
USP51	XM_047441870.1	c.492A>G	p.Arg164Arg	synonymous_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.492A>G	p.Arg164Arg	synonymous_variant	Exon 3 of 3	1	NM_201286.4	ENSP00000423333.2
USP51	ENST00000586165.1	c.123+246A>G		intron_variant	Intron 1 of 1	1		ENSP00000490435.1

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 200 AN: 111798 Hom.: 2 Cov.: 23 AF XY: 0.00147 AC XY: 50 AN XY: 34042

Gnomad AFR AF: 0.000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00793

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.00199

GnomAD3 exomes AF: 0.00217 AC: 387 AN: 177972 Hom.: 1 AF XY: 0.00235 AC XY: 149 AN XY: 63286

Gnomad AFR exome AF: 0.000470

Gnomad AMR exome AF: 0.000921

Gnomad ASJ exome AF: 0.00826

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.00332

Gnomad OTH exome AF: 0.00272

GnomAD4 exome AF: 0.00244 AC: 2673 AN: 1096943 Hom.: 2 Cov.: 36 AF XY: 0.00243 AC XY: 879 AN XY: 362377

Gnomad4 AFR exome AF: 0.000379

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00955

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.00274

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00179 AC: 200 AN: 111841 Hom.: 2 Cov.: 23 AF XY: 0.00147 AC XY: 50 AN XY: 34095

Gnomad4 AFR AF: 0.000324

Gnomad4 AMR AF: 0.00112

Gnomad4 ASJ AF: 0.00793

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.00197

Alfa AF: 0.00327 Hom.: 23

Bravo AF: 0.00182

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs138173648; hg19: chrX-55514881;