Variant 6-99445822-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001346022.3(USP45):c.1950G>T(p.Lys650Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,581,962 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 4 hom. )

Consequence

USP45
NM_001346022.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.713

Variant links:

Genes affected

USP45 (HGNC:20080): (ubiquitin specific peptidase 45) The protein encoded by this gene is a deubiquitylase that binds ERCC1, the catalytic subunit of the XPF-ERCC1 DNA repair endonuclease. This endonuclease is a critical regulator of DNA repair processes, and the deubiquitylase activity of the encoded protein is important for maintaining the DNA repair ability of XPF-ERCC1. [provided by RefSeq, Sep 2016]

USP45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073426664).

BP6

Variant 6-99445822-C-A is Benign according to our data. Variant chr6-99445822-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3047932.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP45	NM_001346022.3 link	c.1950G>T	p.Lys650Asn	missense_variant	Exon 14 of 18	ENST00000500704.7	NP_001332951.1	Q70EL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP45	ENST00000500704.7 link	c.1950G>T	p.Lys650Asn	missense_variant	Exon 14 of 18	5	NM_001346022.3	ENSP00000424372.1		Q70EL2-1

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

264

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00598

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00100

AC:

226

AN:

225174

Hom.:

AF XY:

0.00103

AC XY:

126

AN XY:

121906

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.000726

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00358

Gnomad SAS exome

AF:

0.00221

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000657

AC:

940

AN:

1429812

Hom.:

Cov.:

AF XY:

0.000701

AC XY:

497

AN XY:

709300

show subpopulations

Gnomad4 AFR exome

AF:

0.00583

Gnomad4 AMR exome

AF:

0.000676

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00985

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152150

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00580

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000719

Hom.:

Bravo

AF:

0.00187

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00103

AC:

125

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

USP45-related disorder

Benign:1

May 31, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0029

T;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.83

.;T;T

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.080

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.95

P;P;.

Vest4

0.29

MutPred

0.42

Loss of ubiquitination at K650 (P = 0.0116);Loss of ubiquitination at K650 (P = 0.0116);.;

MVP

0.42

MPC

0.24

ClinPred

0.017

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.069

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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