Genetic Variant USP7:p.Glu19Gly (chr16-8963230-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003470.3(USP7):c.56A>G(p.Glu19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000796 in 1,256,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E19K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

USP7
NM_003470.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16209021).

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.56A>G	p.Glu19Gly	missense	Exon 1 of 31	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+336T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP7	ENST00000344836.9	TSL:1 MANE Select	c.56A>G	p.Glu19Gly	missense	Exon 1 of 31	ENSP00000343535.4	Q93009-1
USP7	ENST00000923082.1		c.56A>G	p.Glu19Gly	missense	Exon 1 of 31	ENSP00000593141.1
USP7	ENST00000923081.1		c.56A>G	p.Glu19Gly	missense	Exon 1 of 31	ENSP00000593140.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

85618

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.96e-7

AC:

AN:

1256466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

620062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24860

American (AMR)

AF:

0.0000399

AC:

AN:

25048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20520

East Asian (EAS)

AF:

0.00

AC:

AN:

23624

South Asian (SAS)

AF:

0.00

AC:

AN:

71036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4210

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1003082

Other (OTH)

AF:

0.00

AC:

AN:

49366

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 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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

2.3

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Uncertain

0.018

Sift4G

Benign

0.18

Polyphen

0.25

Vest4

0.20

MutPred

0.055

Gain of glycosylation at S18 (P = 0.0545)

MVP

0.19

MPC

0.31

ClinPred

0.37

GERP RS

2.5

Varity_R

0.16

gMVP

0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over