rs2238114

Positions:

• chr12-6856576-C-A
• chr12-6856576-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098536.2(USP5):​c.584+126C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,542,150 control chromosomes in the GnomAD database, including 96,648 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (18350 hom., cov: 31)
  • Exomes 𝑓: 0.32 (78298 hom.)
• Consequence: USP5 NM_001098536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

USP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP5	NM_001098536.2	c.584+126C>A		intron_variant		ENST00000229268.13	NP_001092006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP5	ENST00000229268.13	c.584+126C>A		intron_variant		1	NM_001098536.2	ENSP00000229268.8
USP5	ENST00000389231.9	c.584+126C>A		intron_variant		1		ENSP00000373883.5
USP5	ENST00000542087.1	c.357+507C>A		intron_variant		3		ENSP00000444668.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67825 AN: 151864 Hom.: 18305 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.323 AC: 449711 AN: 1390168 Hom.: 78298 Cov.: 30 AF XY: 0.323 AC XY: 221269 AN XY: 685398

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.447 AC: 67935 AN: 151982 Hom.: 18350 Cov.: 31 AF XY: 0.442 AC XY: 32790 AN XY: 74262

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.459

Alfa AF: 0.318 Hom.: 4089

Bravo AF: 0.475

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.025
DANN	Benign	0.46

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: rs2238114; hg19: chr12-6965740; COSMIC: COSV57540679; COSMIC: COSV57540679;