Variant chr6-99437370-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001346022.3(USP45):c.2190C>A(p.Tyr730*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,604,240 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

USP45
NM_001346022.3 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.522

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:

USP45 (HGNC:):

USP45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP45	NM_001346022.3 linkuse as main transcript	c.2190C>A	p.Tyr730*	stop_gained	17/18	ENST00000500704.7	NP_001332951.1	Q70EL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP45	ENST00000500704.7 linkuse as main transcript	c.2190C>A	p.Tyr730*	stop_gained	17/18	5	NM_001346022.3	ENSP00000424372.1		Q70EL2-1

Frequencies

GnomAD3 genomes

AF:

0.000921

AC:

140

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00120

AC:

286

AN:

239192

Hom.:

AF XY:

0.00132

AC XY:

171

AN XY:

129150

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000514

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.00167

AC:

2430

AN:

1452098

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1164

AN XY:

721952

show subpopulations

Gnomad4 AFR exome

AF:

0.000213

Gnomad4 AMR exome

AF:

0.000595

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152142

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000967

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00157

AC:

191

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.12

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.87

Vest4

0.89

GERP RS

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 29

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