Variant 8-143310198-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052963.3(TOP1MT):c.1573C>T(p.Arg525Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,579,896 control chromosomes in the GnomAD database, including 169,713 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 13454 hom., cov: 33)

Exomes 𝑓: 0.46 ( 156259 hom. )

Consequence

TOP1MT
NM_052963.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.176

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.9609944E-6).

BP6

Variant 8-143310198-G-A is Benign according to our data. Variant chr8-143310198-G-A is described in ClinVar as [Benign]. Clinvar id is 1645532.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOP1MT	NM_052963.3 linkuse as main transcript	c.1573C>T	p.Arg525Trp	missense_variant	13/14	ENST00000329245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1MT	ENST00000329245.9 linkuse as main transcript	c.1573C>T	p.Arg525Trp	missense_variant	13/14	1	NM_052963.3	P1	Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57154

AN:

151956

Hom.:

13436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.505

AC:

107399

AN:

212494

Hom.:

29468

AF XY:

0.511

AC XY:

58990

AN XY:

115490

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.682

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.708

Gnomad SAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.457

AC:

652480

AN:

1427822

Hom.:

156259

Cov.:

AF XY:

0.462

AC XY:

326913

AN XY:

707740

show subpopulations

Gnomad4 AFR exome

AF:

0.0806

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.376

AC:

57188

AN:

152074

Hom.:

13454

Cov.:

AF XY:

0.389

AC XY:

28937

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0973

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.683

Gnomad4 SAS

AF:

0.635

Gnomad4 FIN

AF:

0.523

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.390

Alfa

AF:

0.429

Hom.:

13535

Bravo

AF:

0.364

TwinsUK

AF:

0.430

AC:

1593

ALSPAC

AF:

0.450

AC:

1734

ESP6500AA

AF:

0.0987

AC:

434

ESP6500EA

AF:

0.441

AC:

3794

ExAC

AF:

0.470

AC:

56544

Asia WGS

AF:

0.610

AC:

2123

AN:

3478

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.89

D;.;.;D

MetaRNN

Benign

0.0000050

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.019

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.99

D;.;.;.

Vest4

0.12

MPC

0.19

ClinPred

0.043

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.12

gMVP

0.24

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