12-6860158-CTG-TTA

Variant names:

• chr12-6860158-CTG-TTA
• NM_001098536.2:c.1138_1140delCTGinsTTA
• USP5 p.381

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001098536.2(USP5):​c.1138_1140delCTGinsTTA​(p.381) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L380L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP5 NM_001098536.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

USP5 (HGNC:12628): (ubiquitin specific peptidase 5) Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098536.2. 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
	USP5	NM_001098536.2	MANE Select	c.1138_1140delCTGinsTTA	p.381	synonymous	N/A	NP_001092006.1	A0A140VJZ1
	USP5	NM_003481.3		c.1138_1140delCTGinsTTA	p.381	synonymous	N/A	NP_003472.2	P45974-2
	USP5	NM_001382591.1		c.1066_1068delCTGinsTTA	p.357	synonymous	N/A	NP_001369520.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP5	ENST00000229268.13	TSL:1 MANE Select	c.1138_1140delCTGinsTTA	p.381	synonymous	N/A	ENSP00000229268.8	P45974-1
	USP5	ENST00000389231.9	TSL:1	c.1138_1140delCTGinsTTA	p.381	synonymous	N/A	ENSP00000373883.5	P45974-2
	USP5	ENST00000864808.1		c.1138_1140delCTGinsTTA	p.381	synonymous	N/A	ENSP00000534867.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-6969322;