X-47241303-C-T

Variant names:

• chrX-47241303-C-T
• rs151312911
• NM_001371072.1:c.873C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001371072.1(USP11):​c.873C>T​(p.Thr291Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,207,823 control chromosomes in the GnomAD database, including 1 homozygotes. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000080 (1 hom. 44 hem.)
• Consequence: USP11 NM_001371072.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.53
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-47241303-C-T is Benign according to our data. Variant chrX-47241303-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 739635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.53 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 44 gene

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.873C>T	p.Thr291Thr	synonymous	Exon 8 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.873C>T	p.Thr291Thr	synonymous	Exon 8 of 21	ENSP00000366311.2	G5E9A6
	USP11	ENST00000218348.7	TSL:1	c.1002C>T	p.Thr334Thr	synonymous	Exon 8 of 21	ENSP00000218348.3	P51784
	USP11	ENST00000469080.5	TSL:1	n.926C>T		non_coding_transcript_exon	Exon 8 of 19

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111502 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000747

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 21 AN: 179045 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.0000803 AC: 88 AN: 1096321 Hom.: 1 Cov.: 32 AF XY: 0.000122 AC XY: 44 AN XY: 361953

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.00 AC: 0 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19215

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00142 AC: 76 AN: 53693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40456

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4122

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841192

Other (OTH) AF: 0.000152 AC: 7 AN: 46028

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111502 Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1 AN XY: 33666

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30647

American (AMR) AF: 0.00 AC: 0 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.000747 AC: 2 AN: 2678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53064

Other (OTH) AF: 0.00 AC: 0 AN: 1491

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000153 Hom.: 1

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.034
DANN	Benign	0.69
PhyloP100		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151312911; hg19: chrX-47100702; COSMIC: COSV54472297; COSMIC: COSV54472297;