rs749570604

Variant names:

• chr16-8963255-TCTGCTGCTG-T
• rs749570604
• NM_003470.3:c.22_30delCAGCAGCAG

Your query was ambiguous. Multiple possible variants found:

• chr16-8963255-TCTGCTGCTG-T
• chr16-8963255-TCTGCTGCTG-TCTG
• chr16-8963255-TCTGCTGCTG-TCTGCTG
• chr16-8963255-TCTGCTGCTG-TCTGCTGCTGCTG
• chr16-8963255-TCTGCTGCTG-TCTGCTGCTGCTGCTG
• chr16-8963255-TCTGCTGCTG-TCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_003470.3(USP7):​c.22_30delCAGCAGCAG​(p.Gln8_Gln10del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000409 in 1,223,874 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: USP7 NM_003470.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_003470.3

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.22_30delCAGCAGCAG	p.Gln8_Gln10del	conservative_inframe_deletion	Exon 1 of 31	NP_003461.2	Q93009-1
	USP7-AS1	NR_184341.1		n.182+374_182+382delCTGCTGCTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP7	ENST00000344836.9	TSL:1 MANE Select	c.22_30delCAGCAGCAG	p.Gln8_Gln10del	conservative_inframe_deletion	Exon 1 of 31	ENSP00000343535.4	Q93009-1
	USP7	ENST00000923082.1		c.22_30delCAGCAGCAG	p.Gln8_Gln10del	conservative_inframe_deletion	Exon 1 of 31	ENSP00000593141.1
	USP7	ENST00000923081.1		c.22_30delCAGCAGCAG	p.Gln8_Gln10del	conservative_inframe_deletion	Exon 1 of 31	ENSP00000593140.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000409 AC: 5 AN: 1223874 Hom.: 0 AF XY: 0.00000663 AC XY: 4 AN XY: 603546

⚠️ 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: 24352

American (AMR) AF: 0.00 AC: 0 AN: 23696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19612

East Asian (EAS) AF: 0.00 AC: 0 AN: 22508

South Asian (SAS) AF: 0.00 AC: 0 AN: 67224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4060

European-Non Finnish (NFE) AF: 0.00000508 AC: 5 AN: 983786

Other (OTH) AF: 0.00 AC: 0 AN: 47404

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0635184), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

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

Other links and lift over

dbSNP: rs749570604; hg19: chr16-9057112;