USP7 p.Gln4His

Variant names:

• chr16-8963274-C-A
• NM_003470.3:c.12G>T
• USP7 p.Gln4His

Your query was ambiguous. Multiple possible variants found:

• chr16-8963274-C-A
• chr16-8963274-C-G

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.12G>T​(p.Gln4His) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP7 NM_003470.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• 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: 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 (MetaRNN=0.05898431).

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.12G>T	p.Gln4His	missense	Exon 1 of 31	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+380C>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.12G>T	p.Gln4His	missense	Exon 1 of 31	ENSP00000343535.4	Q93009-1
	USP7	ENST00000923082.1		c.12G>T	p.Gln4His	missense	Exon 1 of 31	ENSP00000593141.1
	USP7	ENST00000923081.1		c.12G>T	p.Gln4His	missense	Exon 1 of 31	ENSP00000593140.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1099260 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 541734

African (AFR) AF: 0.00 AC: 0 AN: 21760

American (AMR) AF: 0.00 AC: 0 AN: 19836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16830

East Asian (EAS) AF: 0.00 AC: 0 AN: 18482

South Asian (SAS) AF: 0.00 AC: 0 AN: 58100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 894956

Other (OTH) AF: 0.00 AC: 0 AN: 41574

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.056
Sift	Benign	0.40	T
Sift4G	Benign	0.50	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.033
gMVP		0.36

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-9057131;