rs138367954

Variant names:

• chrX-47242288-G-A
• rs138367954
• NM_001371072.1:c.1386G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-47242288-G-A
• chrX-47242288-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371072.1(USP11):​c.1386G>A​(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,210,278 control chromosomes in the GnomAD database, including 110 homozygotes. There are 1,020 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (11 hom., 95 hem., cov: 23)
  • Exomes 𝑓: 0.0026 (99 hom. 925 hem.)
• Consequence: USP11 NM_001371072.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24
• Publications: 2 publications found

Genes affected

USP11 (HGNC:12609): (ubiquitin specific peptidase 11) Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23 [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-47242288-G-A is Benign according to our data. Variant chrX-47242288-G-A is described in ClinVar as Benign. ClinVar VariationId is 716704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371072.1. 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
	USP11	NM_001371072.1	MANE Select	c.1386G>A	p.Pro462Pro	synonymous	Exon 10 of 21	NP_001358001.1	G5E9A6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP11	ENST00000377107.7	TSL:1 MANE Select	c.1386G>A	p.Pro462Pro	synonymous	Exon 10 of 21	ENSP00000366311.2	G5E9A6
	USP11	ENST00000218348.7	TSL:1	c.1515G>A	p.Pro505Pro	synonymous	Exon 10 of 21	ENSP00000218348.3	P51784
	USP11	ENST00000469080.5	TSL:1	n.1439G>A		non_coding_transcript_exon	Exon 10 of 19

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 325 AN: 112519 Hom.: 11 Cov.: 23

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.00365

Gnomad FIN AF: 0.000648

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000751

Gnomad OTH AF: 0.00863

GnomAD2 exomes AF: 0.00669 AC: 1215 AN: 181725 AF XY: 0.00608

Gnomad AFR exome AF: 0.000384

Gnomad AMR exome AF: 0.000183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0822

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00260 AC: 2855 AN: 1097707 Hom.: 99 Cov.: 32 AF XY: 0.00255 AC XY: 925 AN XY: 363075

African (AFR) AF: 0.000152 AC: 4 AN: 26399

American (AMR) AF: 0.000142 AC: 5 AN: 35177

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.0774 AC: 2337 AN: 30192

South Asian (SAS) AF: 0.000999 AC: 54 AN: 54030

European-Finnish (FIN) AF: 0.00121 AC: 49 AN: 40397

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

European-Non Finnish (NFE) AF: 0.0000641 AC: 54 AN: 841913

Other (OTH) AF: 0.00764 AC: 352 AN: 46081

GnomAD4 genome AF: 0.00287 AC: 323 AN: 112571 Hom.: 11 Cov.: 23 AF XY: 0.00273 AC XY: 95 AN XY: 34739

African (AFR) AF: 0.000387 AC: 12 AN: 31038

American (AMR) AF: 0.00280 AC: 30 AN: 10696

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2651

East Asian (EAS) AF: 0.0698 AC: 249 AN: 3567

South Asian (SAS) AF: 0.00366 AC: 10 AN: 2731

European-Finnish (FIN) AF: 0.000648 AC: 4 AN: 6175

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53284

Other (OTH) AF: 0.00852 AC: 13 AN: 1525

Alfa AF: 0.00109 Hom.: 9

Bravo AF: 0.00345

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.5
DANN	Benign	0.64
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs138367954; hg19: chrX-47101687;