rs12932018

chr16-84762997-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005153.3(USP10):c.1563A>G(p.Gln521=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,602,796 control chromosomes in the GnomAD database, including 59,494 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 0.23 (4780 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54714 hom.)
• Consequence: USP10 NM_005153.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

USP10 (HGNC:12608): (ubiquitin specific peptidase 10) Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.055 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP10	NM_005153.3	c.1563A>G	p.Gln521=	synonymous_variant	9/14	ENST00000219473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP10	ENST00000219473.12	c.1563A>G	p.Gln521=	synonymous_variant	9/14	1	NM_005153.3	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34934 AN: 152040 Hom.: 4773 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.288 AC: 71403 AN: 247846 Hom.: 11495 AF XY: 0.287 AC XY: 38600 AN XY: 134498

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.382

Gnomad SAS exome AF: 0.310

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.268 AC: 388681 AN: 1450638 Hom.: 54714 Cov.: 29 AF XY: 0.270 AC XY: 194767 AN XY: 721720

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.230 AC: 34953 AN: 152158 Hom.: 4780 Cov.: 32 AF XY: 0.231 AC XY: 17210 AN XY: 74378

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.257

Alfa AF: 0.252 Hom.: 4114

Bravo AF: 0.238

Asia WGS AF: 0.309 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	10
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs12932018; hg19: chr16-84796603; COSMIC: COSV54747055; COSMIC: COSV54747055;