rs12932018

Variant names:

• chr16-84762997-A-G
• rs12932018
• NM_005153.3:c.1563A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005153.3(USP10):​c.1563A>G​(p.Gln521Gln) 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 20 publications found

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]

ENSG00000295451 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005153.3. 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
	USP10	NM_005153.3	MANE Select	c.1563A>G	p.Gln521Gln	synonymous	Exon 9 of 14	NP_005144.2	Q14694-1
	USP10	NM_001272075.2		c.1575A>G	p.Gln525Gln	synonymous	Exon 10 of 15	NP_001259004.1	A0A7G6J4N4
	USP10	NR_073577.2		n.552A>G		non_coding_transcript_exon	Exon 7 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP10	ENST00000219473.12	TSL:1 MANE Select	c.1563A>G	p.Gln521Gln	synonymous	Exon 9 of 14	ENSP00000219473.7	Q14694-1
	USP10	ENST00000540269.6	TSL:1	n.*1111A>G		non_coding_transcript_exon	Exon 6 of 11	ENSP00000445589.2	Q68D90
	USP10	ENST00000540269.6	TSL:1	n.*1111A>G		3_prime_UTR	Exon 6 of 11	ENSP00000445589.2	Q68D90

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

GnomAD2 exomes AF: 0.288 AC: 71403 AN: 247846 AF XY: 0.287

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 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

African (AFR) AF: 0.0797 AC: 2659 AN: 33374

American (AMR) AF: 0.450 AC: 19893 AN: 44174

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5840 AN: 25930

East Asian (EAS) AF: 0.360 AC: 14250 AN: 39576

South Asian (SAS) AF: 0.313 AC: 26802 AN: 85534

European-Finnish (FIN) AF: 0.198 AC: 10556 AN: 53180

Middle Eastern (MID) AF: 0.297 AC: 1700 AN: 5716

European-Non Finnish (NFE) AF: 0.264 AC: 290899 AN: 1103350

Other (OTH) AF: 0.269 AC: 16082 AN: 59804

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

African (AFR) AF: 0.0928 AC: 3854 AN: 41532

American (AMR) AF: 0.373 AC: 5700 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1984 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2076 AN: 10580

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18124 AN: 67990

Other (OTH) AF: 0.257 AC: 542 AN: 2110

Alfa AF: 0.254 Hom.: 6170

Bravo AF: 0.238

Asia WGS AF: 0.309 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.38
PhyloP100		0.055
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12932018; hg19: chr16-84796603; COSMIC: COSV54747055; COSMIC: COSV54747055;