NM_003470.3:c.79+9C>T

Variant names:

• chr16-8963198-G-A
• rs1263064586
• NM_003470.3:c.79+9C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003470.3(USP7):​c.79+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000238 in 1,260,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000024 (0 hom.)
• Consequence: USP7 NM_003470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• 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-AS1 (HGNC:55379): (USP7 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

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.79+9C>T		intron	N/A	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+304G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	ENST00000344836.9	TSL:1 MANE Select	c.79+9C>T		intron	N/A	ENSP00000343535.4	Q93009-1
	USP7	ENST00000673704.1		c.184+11896C>T		intron	N/A	ENSP00000501290.1	A0A669KBL1
	USP7	ENST00000923082.1		c.79+9C>T		intron	N/A	ENSP00000593141.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00 AC: 0 AN: 84710 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000238 AC: 3 AN: 1260166 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 621848

African (AFR) AF: 0.00 AC: 0 AN: 24832

American (AMR) AF: 0.00 AC: 0 AN: 24618

Ashkenazi Jewish (ASJ) AF: 0.0000486 AC: 1 AN: 20558

East Asian (EAS) AF: 0.00 AC: 0 AN: 23750

South Asian (SAS) AF: 0.00 AC: 0 AN: 71548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4034

European-Non Finnish (NFE) AF: 9.94e-7 AC: 1 AN: 1005558

Other (OTH) AF: 0.0000202 AC: 1 AN: 49530

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1263064586; hg19: chr16-9057055;