Variant 8-143309558-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052963.3(TOP1MT):c.1704-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,612,382 control chromosomes in the GnomAD database, including 256,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20828 hom., cov: 32)

Exomes 𝑓: 0.56 ( 235376 hom. )

Consequence

TOP1MT
NM_052963.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

TOP1MT (HGNC:29787): (DNA topoisomerase I mitochondrial) This gene encodes a mitochondrial DNA topoisomerase that plays a role in the modification of DNA topology. The encoded protein is a type IB topoisomerase and catalyzes the transient breaking and rejoining of DNA to relieve tension and DNA supercoiling generated in the mitochondrial genome during replication and transcription. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

TOP1MT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 8-143309558-A-G is Benign according to our data. Variant chr8-143309558-A-G is described in ClinVar as [Benign]. Clinvar id is 1599764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP1MT	NM_052963.3 link	c.1704-15T>C		intron_variant		ENST00000329245.9	NP_443195.1	Q969P6-1E5KMK7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP1MT	ENST00000329245.9 link	c.1704-15T>C		intron_variant		1	NM_052963.3	ENSP00000328835.3		Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76469

AN:

151930

Hom.:

20811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.505

GnomAD3 exomes

AF:

0.594

AC:

148563

AN:

249972

Hom.:

46326

AF XY:

0.596

AC XY:

80610

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.803

Gnomad SAS exome

AF:

0.704

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.561

AC:

819400

AN:

1460334

Hom.:

235376

Cov.:

AF XY:

0.565

AC XY:

410188

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.806

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.599

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.503

AC:

76517

AN:

152048

Hom.:

20828

Cov.:

AF XY:

0.513

AC XY:

38152

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.709

Gnomad4 FIN

AF:

0.593

Gnomad4 NFE

AF:

0.548

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.459

Hom.:

2540

Bravo

AF:

0.495

Asia WGS

AF:

0.714

AC:

2484

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.90

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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