USP25 p.Ala610Ala

Variant names:

• chr21-15831463-G-G
• NM_001283041.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr21-15831464--
• chr21-15831466-A-T
• chr21-15831466-A-C
• chr21-15831466-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001283041.3(USP25):​c. variant causes a intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP25 NM_001283041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

Genes affected

USP25 (HGNC:12624): (ubiquitin specific peptidase 25) Ubiquitin (MIM 191339) is a highly conserved 76-amino acid protein involved in regulation of intracellular protein breakdown, cell cycle regulation, and stress response. Ubiquitin is released from degraded proteins by disassembly of the polyubiquitin chains, which is mediated by ubiquitin-specific proteases (USPs), such as USP25 (Valero et al., 1999 [PubMed 10644437]).[supplied by OMIM, Mar 2008]

USP25 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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_001283041.3. 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
	USP25	NM_001283041.3	MANE Select	c.		intron	N/A	NP_001269970.1	Q9UHP3-3
	USP25	NM_001283042.3		c.		intron	N/A	NP_001269971.1	Q9UHP3-1
	USP25	NM_013396.6		c.		intron	N/A	NP_037528.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP25	ENST00000400183.7	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000383044.2	Q9UHP3-3
	USP25	ENST00000285681.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000285681.2	Q9UHP3-1
	USP25	ENST00000285679.10	TSL:1	c.		splice_donor intron	N/A	ENSP00000285679.6	Q9UHP3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

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: chr21-17203782;