Genetic Variant USP7:c.3202+20_3202+21insT (chr16-8894529-C-CA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003470.3(USP7):c.3202+20_3202+21insT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

USP7
NM_003470.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.21

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 Gene-Disease associations (from GenCC):

Hao-Fountain syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, ClinGen
Hao-Fountain syndrome due to USP7 mutation
Inheritance: AD Classification: STRONG Submitted by: G2P

USP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 9 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP7	NM_003470.3	MANE Select	c.3202+20_3202+21insT	intron	N/A	NP_003461.2	Q93009-1
USP7	NM_001286457.2		c.3154+20_3154+21insT	intron	N/A	NP_001273386.2	Q93009-3
USP7	NM_001321858.2		c.3028+20_3028+21insT	intron	N/A	NP_001308787.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP7	ENST00000344836.9	TSL:1 MANE Select	c.3202+20_3202+21insT	intron	N/A	ENSP00000343535.4	Q93009-1
USP7	ENST00000381886.8	TSL:1	c.3154+20_3154+21insT	intron	N/A	ENSP00000371310.4	Q93009-3
USP7	ENST00000673704.1		c.3307+20_3307+21insT	intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

150996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000927

AC:

124

AN:

1337046

Hom.:

Cov.:

AF XY:

0.0000902

AC XY:

AN XY:

665404

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31884

American (AMR)

AF:

0.00

AC:

AN:

40896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24034

East Asian (EAS)

AF:

0.00

AC:

AN:

35286

South Asian (SAS)

AF:

0.0000390

AC:

AN:

76936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3902

European-Non Finnish (NFE)

AF:

0.000114

AC:

117

AN:

1022730

Other (OTH)

AF:

0.0000541

AC:

AN:

55416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

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:

0.0000596

AC:

AN:

150996

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73646

show subpopulations

African (AFR)

AF:

0.0000975

AC:

AN:

41016

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000738

AC:

AN:

67756

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000153

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.2

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

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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