11-113799400-C-T

Position:

• chr11-113799400-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346252.4(USP28):​c.3260G>A​(p.Cys1087Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP28 NM_001346252.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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]

USP28 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21821925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP28	NM_001346252.4	c.3260G>A	p.Cys1087Tyr	missense_variant	26/26	ENST00000696973.1	NP_001333181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP28	ENST00000696973.1	c.3260G>A	p.Cys1087Tyr	missense_variant	26/26		NM_001346252.4	ENSP00000513009.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

The c.3074G>A (p.C1025Y) alteration is located in exon 25 (coding exon 25) of the USP28 gene. This alteration results from a G to A substitution at nucleotide position 3074, causing the cysteine (C) at amino acid position 1025 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.087
Sift	Benign	0.036	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.36	B;P;P
Vest4		0.30
MutPred		0.46		Loss of catalytic residue at L1026 (P = 0.011);.;.;
MVP		0.54
MPC		0.37
ClinPred		0.66	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-113670122;