dbSNP rs3214650: USP7:c.3202+18_3202+20delCCC (chr16-8894529-CGGG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003470.3(USP7):c.3202+18_3202+20delCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,044 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

USP7
NM_003470.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

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 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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+18_3202+20delCCC	intron	N/A	NP_003461.2	Q93009-1
USP7	NM_001286457.2		c.3154+18_3154+20delCCC	intron	N/A	NP_001273386.2	Q93009-3
USP7	NM_001321858.2		c.3028+18_3028+20delCCC	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+18_3202+20delCCC	intron	N/A	ENSP00000343535.4	Q93009-1
USP7	ENST00000381886.8	TSL:1	c.3154+18_3154+20delCCC	intron	N/A	ENSP00000371310.4	Q93009-3
USP7	ENST00000673704.1		c.3307+18_3307+20delCCC	intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.48e-7

AC:

AN:

1337044

Hom.:

AF XY:

0.00

AC XY:

AN XY:

665404

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

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:

0.00

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:

9.78e-7

AC:

AN:

1022728

Other (OTH)

AF:

0.00

AC:

AN:

55416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over