Genetic Variant USP10:p.Gln521Gln (chr16-84762997-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

20 publications found

Variant links:

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]

USP10 links:

ENSG00000295451 (HGNC:):

ENSG00000295451 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP10	NM_005153.3 link	c.1563A>G	p.Gln521Gln	synonymous_variant	Exon 9 of 14	ENST00000219473.12	NP_005144.2	Q14694-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP10	ENST00000219473.12 link	c.1563A>G	p.Gln521Gln	synonymous_variant	Exon 9 of 14	1	NM_005153.3	ENSP00000219473.7		Q14694-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34934

AN:

152040

Hom.:

4773

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.270

AC XY:

194767

AN XY:

721720

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

11549

23098

34647

46196

57745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9856

19712

29568

39424

49280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.230

AC:

34953

AN:

152158

Hom.:

4780

Cov.:

AF XY:

0.231

AC XY:

17210

AN XY:

74378

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.38

PhyloP100

0.055

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over