Genetic Variant USP10:c.21+9161C>T (chr16-84709272-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005153.3(USP10):c.21+9161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,984 control chromosomes in the GnomAD database, including 20,937 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 0.52 ( 20931 hom., cov: 31)

Exomes 𝑓: 0.50 ( 6 hom. )

Consequence

USP10
NM_005153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.572

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP10	NM_005153.3	MANE Select	c.21+9161C>T	intron	N/A	NP_005144.2	Q14694-1
USP10	NM_001272075.2		c.33+4412C>T	intron	N/A	NP_001259004.1	A0A7G6J4N4
USP10	NR_073577.2		n.112+9161C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP10	ENST00000219473.12	TSL:1 MANE Select	c.21+9161C>T	intron	N/A	ENSP00000219473.7	Q14694-1
USP10	ENST00000540269.6	TSL:1	n.21+9161C>T	intron	N/A	ENSP00000445589.2	Q68D90
USP10	ENST00000933625.1		c.21+9161C>T	intron	N/A	ENSP00000603684.1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79100

AN:

151834

Hom.:

20904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.538

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.714

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.521

AC:

79178

AN:

151954

Hom.:

20931

Cov.:

AF XY:

0.519

AC XY:

38559

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.517

AC:

21438

AN:

41440

American (AMR)

AF:

0.359

AC:

5487

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1749

AN:

3472

East Asian (EAS)

AF:

0.478

AC:

2464

AN:

5154

South Asian (SAS)

AF:

0.536

AC:

2577

AN:

4810

European-Finnish (FIN)

AF:

0.596

AC:

6283

AN:

10550

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.553

AC:

37567

AN:

67954

Other (OTH)

AF:

0.501

AC:

1055

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1953

3906

5859

7812

9765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.531

Hom.:

57513

Bravo

AF:

0.502

Asia WGS

AF:

0.519

AC:

1806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.2

(source)

DANN

Benign

0.57

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over