Variant 22-21957428-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001282112.2(TOP3B):c.2275G>A(p.Glu759Lys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TOP3B
NM_001282112.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.88

Variant links:

Genes affected

TOP3B (HGNC:11993): (DNA topoisomerase III beta) This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Low expression of this gene may be related to higher survival rates in breast cancer patients. This gene has a pseudogene on chromosome 22. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]

TOP3B links:

PPM1F-AS1 (HGNC:40888): (PPM1F antisense RNA 1)

PPM1F-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021692932).

BP6

Variant 22-21957428-C-T is Benign according to our data. Variant chr22-21957428-C-T is described in ClinVar as [Benign]. Clinvar id is 2652951.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP3B	NM_001282112.2 linkuse as main transcript	c.2275G>A	p.Glu759Lys	missense_variant	18/18	ENST00000357179.10	NP_001269041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP3B	ENST00000357179.10 linkuse as main transcript	c.2275G>A	p.Glu759Lys	missense_variant	18/18	1	NM_001282112.2	ENSP00000349705	P1	O95985-1
PPM1F-AS1	ENST00000458178.2 linkuse as main transcript	n.17648C>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

154

AN:

143748

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.00103

GnomAD3 exomes

AF:

0.000920

AC:

125

AN:

135822

Hom.:

AF XY:

0.000907

AC XY:

AN XY:

73850

show subpopulations

Gnomad AFR exome

AF:

0.000298

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.000260

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00127

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00135

AC:

1561

AN:

1159012

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

782

AN XY:

584392

show subpopulations

Gnomad4 AFR exome

AF:

0.000217

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.000127

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00107

AC:

154

AN:

143824

Hom.:

Cov.:

AF XY:

0.000948

AC XY:

AN XY:

69602

show subpopulations

Gnomad4 AFR

AF:

0.000230

Gnomad4 AMR

AF:

0.00195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000102

Gnomad4 NFE

AF:

0.00175

Gnomad4 OTH

AF:

0.00102

Alfa

AF:

0.000948

Hom.:

Bravo

AF:

0.00106

ExAC

AF:

0.000421

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

TOP3B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

0.011

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.11

Sift

Benign

0.20

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.22

B;B

Vest4

0.41

MVP

0.74

MPC

2.1

ClinPred

0.045

GERP RS

4.6

Varity_R

0.29

gMVP

0.51

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