NM_015276.2:c.1297G>A

Variant names:

• chr17-21006921-C-T
• rs1913800107
• NM_015276.2:c.1297G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015276.2(USP22):​c.1297G>A​(p.Asp433Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP22 NM_015276.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937

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.1297G>A	p.Asp433Asn	missense	Exon 10 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.1297G>A	p.Asp433Asn	missense	Exon 10 of 13	ENSP00000261497.4	Q9UPT9-1
	USP22	ENST00000537526.6	TSL:1	c.1261G>A	p.Asp421Asn	missense	Exon 10 of 13	ENSP00000440950.2	Q9UPT9-2
	USP22	ENST00000478443.1	TSL:1	n.658G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.82		Gain of sheet (P = 0.1208)
MVP		0.60
MPC		2.0
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1913800107; hg19: chr17-20910234;