chr17-21042717-G-C

Variant names:

• chr17-21042717-G-C
• rs1335080565
• NM_015276.2:c.119C>G

Variant summary

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

The NM_015276.2(USP22):​c.119C>G​(p.Ala40Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP22 NM_015276.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

Genes affected

USP22 (HGNC:12621): (ubiquitin specific peptidase 22) Enables enzyme binding activity; nuclear receptor coactivator activity; and thiol-dependent deubiquitinase. Contributes to H4 histone acetyltransferase activity. Involved in positive regulation of mitotic cell cycle; positive regulation of transcription, DNA-templated; and protein modification by small protein conjugation or removal. Part of SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.13648257).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015276.2. 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
	USP22	NM_015276.2	MANE Select	c.119C>G	p.Ala40Gly	missense	Exon 1 of 13	NP_056091.1	Q9UPT9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP22	ENST00000261497.9	TSL:1 MANE Select	c.119C>G	p.Ala40Gly	missense	Exon 1 of 13	ENSP00000261497.4	Q9UPT9-1
	USP22	ENST00000537526.6	TSL:1	c.135+909C>G		intron	N/A	ENSP00000440950.2	Q9UPT9-2
	USP22	ENST00000952978.1		c.119C>G	p.Ala40Gly	missense	Exon 1 of 14	ENSP00000623037.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1301304 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 640352

African (AFR) AF: 0.00 AC: 0 AN: 27498

American (AMR) AF: 0.00 AC: 0 AN: 29924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22188

East Asian (EAS) AF: 0.00 AC: 0 AN: 30322

South Asian (SAS) AF: 0.00 AC: 0 AN: 69722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028314

Other (OTH) AF: 0.00 AC: 0 AN: 52910

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.066
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.39		Gain of sheet (P = 0.1208)
MVP		0.15
MPC		0.91
ClinPred		0.30	T
GERP RS		0.40
PromoterAI		-0.027	Neutral
Varity_R		0.12
gMVP		0.42

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: rs1335080565; hg19: chr17-20946030;