Genetic Variant USP7:p.Gln10dup (chr16-8963255-T-TCTG) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_003470.3(USP7):c.28_30dupCAG(p.Gln10dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,373,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

USP7
NM_003470.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.54

Publications

1 publications found

Variant links:

Genes affected

USP7 (HGNC:12630): (ubiquitin specific peptidase 7) The protein encoded by this gene belongs to the peptidase C19 family, which includes ubiquitinyl hydrolases. This protein deubiquitinates target proteins such as p53 (a tumor suppressor protein) and WASH (essential for endosomal protein recycling), and regulates their activities by counteracting the opposing ubiquitin ligase activity of proteins such as HDM2 and TRIM27, involved in the respective process. Mutations in this gene have been implicated in a neurodevelopmental disorder. [provided by RefSeq, Mar 2016]

USP7 links:

USP7-AS1 (HGNC:55379): (USP7 antisense RNA 1)

USP7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003470.3

BP6

Variant 16-8963255-T-TCTG is Benign according to our data. Variant chr16-8963255-T-TCTG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2056639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 79 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003470.3. 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
	USP7	NM_003470.3	MANE Select	c.28_30dupCAG	p.Gln10dup	conservative_inframe_insertion	Exon 1 of 31	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+380_182+382dupCTG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP7	ENST00000344836.9	TSL:1 MANE Select	c.28_30dupCAG	p.Gln10dup	conservative_inframe_insertion	Exon 1 of 31	ENSP00000343535.4	Q93009-1
USP7	ENST00000923082.1		c.28_30dupCAG	p.Gln10dup	conservative_inframe_insertion	Exon 1 of 31	ENSP00000593141.1
USP7	ENST00000923081.1		c.28_30dupCAG	p.Gln10dup	conservative_inframe_insertion	Exon 1 of 31	ENSP00000593140.1

Frequencies

GnomAD3 genomes

AF:

0.000509

AC:

AN:

149188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00497

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000373

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000285

AC:

AN:

77186

AF XY:

0.000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000426

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.000159

Gnomad NFE exome

AF:

0.000354

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.000334

AC:

409

AN:

1223842

Hom.:

Cov.:

AF XY:

0.000313

AC XY:

189

AN XY:

603530

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

24350

American (AMR)

AF:

0.000295

AC:

AN:

23694

Ashkenazi Jewish (ASJ)

AF:

0.0000510

AC:

AN:

19614

East Asian (EAS)

AF:

0.00702

AC:

158

AN:

22508

South Asian (SAS)

AF:

0.000268

AC:

AN:

67218

European-Finnish (FIN)

AF:

0.0000320

AC:

AN:

31230

Middle Eastern (MID)

AF:

0.00148

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.000189

AC:

186

AN:

983764

Other (OTH)

AF:

0.000338

AC:

AN:

47404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000529

AC:

AN:

149272

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

AN XY:

72894

show subpopulations

African (AFR)

AF:

0.000511

AC:

AN:

41070

American (AMR)

AF:

0.000398

AC:

AN:

15062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00499

AC:

AN:

5014

South Asian (SAS)

AF:

0.000209

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.000105

AC:

AN:

9534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000373

AC:

AN:

67102

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000540

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

USP7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-8963255-TCTGCTGCTG-TCTGCTGCTGCTG

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