chr16-8894529-C-CGGGG

Variant names:

• chr16-8894529-C-CGGGG
• rs3214650
• NM_003470.3:c.3202+17_3202+20dupCCCC

Variant summary

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

The NM_003470.3(USP7):​c.3202+17_3202+20dupCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000015 (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: Uncertain_significance. The variant received 0 ACMG points.

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+17_3202+20dupCCCC		intron	N/A	NP_003461.2	Q93009-1
	USP7	NM_001286457.2		c.3154+17_3154+20dupCCCC		intron	N/A	NP_001273386.2	Q93009-3
	USP7	NM_001321858.2		c.3028+17_3028+20dupCCCC		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+20_3202+21insCCCC		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000381886.8	TSL:1	c.3154+20_3154+21insCCCC		intron	N/A	ENSP00000371310.4	Q93009-3
	USP7	ENST00000673704.1		c.3307+20_3307+21insCCCC		intron	N/A	ENSP00000501290.1	A0A669KBL1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1337042 Hom.: 0 Cov.: 0 AF XY: 0.00000301 AC XY: 2 AN XY: 665402

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

African (AFR) AF: 0.00 AC: 0 AN: 31884

American (AMR) AF: 0.0000245 AC: 1 AN: 40896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24034

East Asian (EAS) AF: 0.00 AC: 0 AN: 35284

South Asian (SAS) AF: 0.00 AC: 0 AN: 76936

European-Finnish (FIN) AF: 0.0000218 AC: 1 AN: 45962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3902

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022728

Other (OTH) AF: 0.00 AC: 0 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.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 1411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3214650; hg19: chr16-8988386;