Variant 1-62445065-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003368.5(USP1):c.885G>T(p.Glu295Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

USP1
NM_003368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.219

Variant links:

Genes affected

USP1 (HGNC:12607): (ubiquitin specific peptidase 1) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. The protein specifically deubiquitinates a protein in the Fanconi anemia (FA) DNA repair pathway. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

USP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18104717).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP1	NM_003368.5 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	6/9	ENST00000339950.5	NP_003359.3	O94782
USP1	NM_001017415.2 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	6/9		NP_001017415.1	O94782
USP1	NM_001017416.2 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	6/9		NP_001017416.1	O94782

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP1	ENST00000339950.5 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	6/9	1	NM_003368.5	ENSP00000343526.4		O94782
USP1	ENST00000371146.5 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	6/9	5		ENSP00000360188.1		O94782

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248122

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460132

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.885G>T (p.E295D) alteration is located in exon 6 (coding exon 5) of the USP1 gene. This alteration results from a G to T substitution at nucleotide position 885, causing the glutamic acid (E) at amino acid position 295 to be replaced by an aspartic acid (D). 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

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

T;.

M_CAP

Benign

0.0061

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.087

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.033

D;D

Polyphen

1.0

D;D

Vest4

0.099

MutPred

0.32

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.50

MPC

0.10

ClinPred

0.47

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over