rs193920846

Variant names:

• chr11-113834299-G-A
• rs193920846
• NM_001346252.4:c.571C>T

Variant summary

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

The NM_001346252.4(USP28):​c.571C>T​(p.Leu191Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP28 NM_001346252.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.14
• Publications: 1 publications found

Genes affected

USP28 (HGNC:12625): (ubiquitin specific peptidase 28) The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346252.4. 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
	USP28	NM_001346252.4	MANE Select	c.571C>T	p.Leu191Phe	missense	Exon 6 of 26	NP_001333181.1	A0A8V8TLZ9
	USP28	NM_001400785.1		c.571C>T	p.Leu191Phe	missense	Exon 6 of 26	NP_001387714.1
	USP28	NM_001400784.1		c.493C>T	p.Leu165Phe	missense	Exon 5 of 25	NP_001387713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP28	ENST00000696973.1	MANE Select	c.571C>T	p.Leu191Phe	missense	Exon 6 of 26	ENSP00000513009.1	A0A8V8TLZ9
	USP28	ENST00000003302.8	TSL:1	c.571C>T	p.Leu191Phe	missense	Exon 6 of 25	ENSP00000003302.4	Q96RU2-1
	USP28	ENST00000537706.5	TSL:1	c.571C>T	p.Leu191Phe	missense	Exon 6 of 15	ENSP00000445743.1	Q96RU2-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.69		Gain of helix (P = 0.2294)
MVP		0.80
MPC		0.75
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.61
gMVP		0.58
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs193920846; hg19: chr11-113705021; COSMIC: COSV50202351; COSMIC: COSV50202351;