16-8897333-G-T

Variant names:

• chr16-8897333-G-T
• rs1529916
• NM_003470.3:c.2719-234C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003470.3(USP7):​c.2719-234C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 12 publications found

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, ClinGen, Illumina
• Hao-Fountain syndrome due to USP7 mutation

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP7	NM_003470.3	c.2719-234C>A		intron_variant	Intron 25 of 30	ENST00000344836.9	NP_003461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP7	ENST00000344836.9	c.2719-234C>A		intron_variant	Intron 25 of 30	1	NM_003470.3	ENSP00000343535.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 333112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 175104

African (AFR) AF: 0.00 AC: 0 AN: 10032

American (AMR) AF: 0.00 AC: 0 AN: 11548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10224

East Asian (EAS) AF: 0.00 AC: 0 AN: 23282

South Asian (SAS) AF: 0.00 AC: 0 AN: 29702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1496

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 204802

Other (OTH) AF: 0.00 AC: 0 AN: 19364

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1851

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-0.40

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

Other links and lift over

dbSNP: rs1529916; hg19: chr16-8991190;