Genetic Variant NM_003470.3:c.60C>T (chr16-8963226-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003470.3(USP7):c.60C>T(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,409,262 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 30)

Exomes 𝑓: 0.0059 ( 69 hom. )

Consequence

USP7
NM_003470.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.484

Publications

3 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 16-8963226-G-A is Benign according to our data. Variant chr16-8963226-G-A is described in ClinVar as Benign. ClinVar VariationId is 2043545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.484 with no splicing effect.

BS2

High AC in GnomAd4 at 734 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.60C>T	p.Pro20Pro	synonymous	Exon 1 of 31	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+332G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP7	ENST00000344836.9	TSL:1 MANE Select	c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 31	ENSP00000343535.4	Q93009-1
USP7	ENST00000923082.1		c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 31	ENSP00000593141.1
USP7	ENST00000923081.1		c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 31	ENSP00000593140.1

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

736

AN:

150356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00192

Gnomad ASJ

AF:

0.0483

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00916

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.0321

Gnomad NFE

AF:

0.00603

Gnomad OTH

AF:

0.0112

GnomAD2 exomes

AF:

0.00907

AC:

777

AN:

85666

AF XY:

0.00966

show subpopulations

Gnomad AFR exome

AF:

0.00300

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.0470

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00173

Gnomad NFE exome

AF:

0.00679

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.00592

AC:

7446

AN:

1258806

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

3936

AN XY:

621224

show subpopulations

African (AFR)

AF:

0.000562

AC:

AN:

24906

American (AMR)

AF:

0.00124

AC:

AN:

25006

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

929

AN:

20542

East Asian (EAS)

AF:

0.00

AC:

AN:

23782

South Asian (SAS)

AF:

0.0111

AC:

787

AN:

71112

European-Finnish (FIN)

AF:

0.00165

AC:

AN:

35136

Middle Eastern (MID)

AF:

0.0180

AC:

AN:

4158

European-Non Finnish (NFE)

AF:

0.00514

AC:

5164

AN:

1004636

Other (OTH)

AF:

0.00783

AC:

388

AN:

49528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

312

624

935

1247

1559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<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:

0.00488

AC:

734

AN:

150456

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

354

AN XY:

73512

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

41314

American (AMR)

AF:

0.00192

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.0483

AC:

167

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5050

South Asian (SAS)

AF:

0.00938

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00120

AC:

AN:

9966

Middle Eastern (MID)

AF:

0.0276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00603

AC:

407

AN:

67462

Other (OTH)

AF:

0.0106

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.00455

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.48

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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