Variant 6-99446062-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001346022.3(USP45):c.1710A>G(p.Gly570=) 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

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:

TSTD3 (HGNC:40910): (thiosulfate sulfurtransferase like domain containing 3)

TSTD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
USP45	NM_001346022.3 linkuse as main transcript	c.1710A>G	p.Gly570=	synonymous_variant	14/18	ENST00000500704.7	NP_001332951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP45	ENST00000500704.7 linkuse as main transcript	c.1710A>G	p.Gly570=	synonymous_variant	14/18	5	NM_001346022.3	ENSP00000424372	P1	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

GnomAD3 exomes

AF:

0.339

AC:

85045

AN:

250724

Hom.:

15263

AF XY:

0.343

AC XY:

46454

AN XY:

135606

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 SAS exome

AF:

0.415

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

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.427

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.292

AC:

44339

AN:

152060

Hom.:

6729

Cov.:

AF XY:

0.294

AC XY:

21847

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.480

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.307

Hom.:

17533

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.3

DANN

Benign

0.52

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