Genetic Variant NM_003470.3:c.28_30delCAG (chr16-8963255-TCTG-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003470.3(USP7):c.28_30delCAG(p.Gln10del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,363,576 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

USP7
NM_003470.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 3.39

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 1482 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP7	NM_003470.3 link	c.28_30delCAG	p.Gln10del	conservative_inframe_deletion	Exon 1 of 31	ENST00000344836.9	NP_003461.2	Q93009-1Q6U8A4
USP7-AS1	NR_184341.1 link	n.182+380_182+382delCTG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP7	ENST00000344836.9 link	c.28_30delCAG	p.Gln10del	conservative_inframe_deletion	Exon 1 of 31	1	NM_003470.3	ENSP00000343535.4		Q93009-1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00122

AC:

1482

AN:

1214320

Hom.:

AF XY:

0.00129

AC XY:

772

AN XY:

598308

show subpopulations

Gnomad4 AFR exome

AF:

0.000868

Gnomad4 AMR exome

AF:

0.00234

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.00288

Gnomad4 FIN exome

AF:

0.00330

Gnomad4 NFE exome

AF:

0.000991

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149256

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72888

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000105

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.28_30del, results in the deletion of 1 amino acid(s) of the USP7 protein (p.Gln10del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with USP7-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

USP7-related disorder

Benign:1

Dec 14, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over