16-8894530-G-A

Variant names:

• chr16-8894530-G-A
• rs530879035
• NM_003470.3:c.3202+20C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003470.3(USP7):​c.3202+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 0)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 0 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, Illumina, ClinGen
• Hao-Fountain syndrome due to USP7 mutation

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAdExome4 at 8 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	NM_003470.3	MANE Select	c.3202+20C>T		intron	N/A	NP_003461.2	Q93009-1
	USP7	NM_001286457.2		c.3154+20C>T		intron	N/A	NP_001273386.2	Q93009-3
	USP7	NM_001321858.2		c.3028+20C>T		intron	N/A	NP_001308787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	ENST00000344836.9	TSL:1 MANE Select	c.3202+20C>T		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000381886.8	TSL:1	c.3154+20C>T		intron	N/A	ENSP00000371310.4	Q93009-3
	USP7	ENST00000673704.1		c.3307+20C>T		intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000251 AC: 3 AN: 119738 AF XY: 0.0000309

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: 0.0000539

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000156 AC: 8 AN: 513210 Hom.: 0 Cov.: 0 AF XY: 0.0000234 AC XY: 6 AN XY: 256034

African (AFR) AF: 0.0000611 AC: 1 AN: 16358

American (AMR) AF: 0.00 AC: 0 AN: 12552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8772

East Asian (EAS) AF: 0.00 AC: 0 AN: 20192

South Asian (SAS) AF: 0.00 AC: 0 AN: 35856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1470

European-Non Finnish (NFE) AF: 0.0000160 AC: 6 AN: 375740

Other (OTH) AF: 0.0000451 AC: 1 AN: 22172

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.40
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs530879035; hg19: chr16-8988387;