Variant 22-21957510-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001282112.2(TOP3B):c.2193C>T(p.Ser731=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 1078 hom., cov: 17)

Exomes 𝑓: 0.30 ( 9968 hom. )

Failed GnomAD Quality Control

Consequence

TOP3B
NM_001282112.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.99

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-21957510-G-A is Benign according to our data. Variant chr22-21957510-G-A is described in ClinVar as [Benign]. Clinvar id is 770011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.99 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP3B	NM_001282112.2 linkuse as main transcript	c.2193C>T	p.Ser731=	synonymous_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.2193C>T	p.Ser731=	synonymous_variant	18/18	1	NM_001282112.2	ENSP00000349705	P1	O95985-1
PPM1F-AS1	ENST00000458178.2 linkuse as main transcript	n.17730G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

30543

AN:

109466

Hom.:

1076

Cov.:

FAILED QC

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.205

AC:

18064

AN:

87952

Hom.:

900

AF XY:

0.204

AC XY:

9571

AN XY:

47004

show subpopulations

Gnomad AFR exome

AF:

0.0949

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.302

AC:

215523

AN:

714000

Hom.:

9968

Cov.:

AF XY:

0.296

AC XY:

107396

AN XY:

362998

show subpopulations

Gnomad4 AFR exome

AF:

0.0912

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.279

AC:

30540

AN:

109556

Hom.:

1078

Cov.:

AF XY:

0.278

AC XY:

14549

AN XY:

52326

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.259

Hom.:

284

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 30, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.58

DANN

Benign

0.86

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