rs193920846

chr11-113834299-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP28	NM_001346252.4	c.571C>T	p.Leu191Phe	missense_variant	6/26	ENST00000696973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP28	ENST00000696973.1	c.571C>T	p.Leu191Phe	missense_variant	6/26		NM_001346252.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.1	M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.48
MutPred		0.69		Gain of helix (P = 0.2294);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920846; hg19: chr11-113705021; COSMIC: COSV50202351; COSMIC: COSV50202351;