rs112157723

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

6 publications found

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:

PNISR-AS1 (HGNC:40958): (PNISR antisense RNA 1)

PNISR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3047932.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346022.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP45	NM_001346022.3	MANE Select	c.1950G>T	p.Lys650Asn	missense	Exon 14 of 18	NP_001332951.1	Q70EL2-1
USP45	NM_001080481.3		c.1950G>T	p.Lys650Asn	missense	Exon 14 of 18	NP_001073950.1	Q70EL2-1
USP45	NM_001346021.3		c.1950G>T	p.Lys650Asn	missense	Exon 14 of 18	NP_001332950.1	Q70EL2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP45	ENST00000500704.7	TSL:5 MANE Select	c.1950G>T	p.Lys650Asn	missense	Exon 14 of 18	ENSP00000424372.1	Q70EL2-1
USP45	ENST00000327681.10	TSL:1	c.1950G>T	p.Lys650Asn	missense	Exon 14 of 18	ENSP00000333376.6	Q70EL2-1
USP45	ENST00000496518.6	TSL:1	n.*916G>T		non_coding_transcript_exon	Exon 9 of 13	ENSP00000421248.1	H0Y8J5

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

GnomAD2 exomes

AF:

0.00100

AC:

226

AN:

225174

AF XY:

0.00103

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 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

African (AFR)

AF:

0.00583

AC:

185

AN:

31752

American (AMR)

AF:

0.000676

AC:

AN:

36980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24508

East Asian (EAS)

AF:

0.00985

AC:

388

AN:

39380

South Asian (SAS)

AF:

0.00183

AC:

147

AN:

80150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52240

Middle Eastern (MID)

AF:

0.00128

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.0000981

AC:

108

AN:

1100442

Other (OTH)

AF:

0.00136

AC:

AN:

58908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152150

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00503

AC:

209

AN:

41528

American (AMR)

AF:

0.00118

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00580

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00101

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

USP45-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

0.71

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.080

Sift

Benign

0.26

Sift4G

Benign

0.39

Polyphen

0.95

Vest4

0.29

MutPred

0.42

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

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over