X-47242288-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001371072.1(USP11):​c.1386G>C​(p.Pro462Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P462P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: USP11 NM_001371072.1 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.

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>C	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>C	p.Pro462Pro	synonymous	Exon 10 of 21	ENSP00000366311.2	G5E9A6
	USP11	ENST00000218348.7	TSL:1	c.1515G>C	p.Pro505Pro	synonymous	Exon 10 of 21	ENSP00000218348.3	P51784
	USP11	ENST00000469080.5	TSL:1	n.1439G>C		non_coding_transcript_exon	Exon 10 of 19

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097708 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363076

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35177

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 30193

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40397

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841913

Other (OTH) AF: 0.00 AC: 0 AN: 46081

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.5
DANN	Benign	0.53
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;