Genetic Variant USP45:p.Gly570Gly (chr6-99446062-T-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001346022.3(USP45):c.1710A>G(p.Gly570Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,670 control chromosomes in the GnomAD database, including 77,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6729 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70622 hom. )

Consequence

USP45
NM_001346022.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.186

Publications

27 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-99446062-T-C is Benign according to our data. Variant chr6-99446062-T-C is described in ClinVar as [Benign]. Clinvar id is 1684199.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.186 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP45	NM_001346022.3 link	c.1710A>G	p.Gly570Gly	synonymous_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.1710A>G	p.Gly570Gly	synonymous_variant	Exon 14 of 18	5	NM_001346022.3	ENSP00000424372.1		Q70EL2-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44334

AN:

151942

Hom.:

6735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.309

GnomAD2 exomes

AF:

0.339

AC:

85045

AN:

250724

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.511

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.306

AC:

447507

AN:

1461610

Hom.:

70622

Cov.:

AF XY:

0.309

AC XY:

224829

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.236

AC:

7916

AN:

33474

American (AMR)

AF:

0.381

AC:

17034

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

9191

AN:

26130

East Asian (EAS)

AF:

0.427

AC:

16968

AN:

39696

South Asian (SAS)

AF:

0.412

AC:

35561

AN:

86244

European-Finnish (FIN)

AF:

0.305

AC:

16248

AN:

53250

Middle Eastern (MID)

AF:

0.387

AC:

2233

AN:

5768

European-Non Finnish (NFE)

AF:

0.290

AC:

322872

AN:

1111944

Other (OTH)

AF:

0.323

AC:

19484

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17584

35168

52751

70335

87919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.292

AC:

44339

AN:

152060

Hom.:

6729

Cov.:

AF XY:

0.294

AC XY:

21847

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.230

AC:

9559

AN:

41486

American (AMR)

AF:

0.315

AC:

4806

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1244

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2486

AN:

5174

South Asian (SAS)

AF:

0.416

AC:

2004

AN:

4812

European-Finnish (FIN)

AF:

0.295

AC:

3120

AN:

10564

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20080

AN:

67968

Other (OTH)

AF:

0.313

AC:

662

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1618

3236

4855

6473

8091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.307

Hom.:

23591

Bravo

AF:

0.294

Asia WGS

AF:

0.447

AC:

1553

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 19

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.3

(source)

DANN

Benign

0.52

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr6-99446062-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over