X-47239077-G-T

Variant names:

• chrX-47239077-G-T
• rs183062376
• NM_001371072.1:c.184G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371072.1(USP11):​c.184G>T​(p.Val62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,279 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: USP11 NM_001371072.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16643181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP11	NM_001371072.1	c.184G>T	p.Val62Leu	missense_variant	Exon 2 of 21	ENST00000377107.7	NP_001358001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP11	ENST00000377107.7	c.184G>T	p.Val62Leu	missense_variant	Exon 2 of 21	1	NM_001371072.1	ENSP00000366311.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000115 AC: 2 AN: 174191 Hom.: 0 AF XY: 0.0000167 AC XY: 1 AN XY: 59769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000745

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095279 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 360917

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000571

Gnomad4 ASJ exome AF: 0.0000518

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.074
Sift	Benign	0.14	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.015	.;B
Vest4		0.14
MutPred		0.51		.;Gain of sheet (P = 0.0477);
MVP		0.72
MPC		0.71
ClinPred		0.19	T
GERP RS		5.0
Varity_R		0.49
gMVP		0.83

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: rs183062376; hg19: chrX-47098476;