Variant 8-143321315-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_052963.3(TOP1MT):c.1032C>G(p.Arg344=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,609,856 control chromosomes in the GnomAD database, including 69,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8709 hom., cov: 34)

Exomes 𝑓: 0.28 ( 60779 hom. )

Consequence

TOP1MT
NM_052963.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.49

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 -21 ACMG points.

BP4

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

BP6

Variant 8-143321315-G-C is Benign according to our data. Variant chr8-143321315-G-C is described in ClinVar as [Benign]. Clinvar id is 1645543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 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.1032C>G	p.Arg344=	synonymous_variant	8/14	ENST00000329245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1MT	ENST00000329245.9 linkuse as main transcript	c.1032C>G	p.Arg344=	synonymous_variant	8/14	1	NM_052963.3	P1	Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48976

AN:

152008

Hom.:

8702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.0743

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.326

GnomAD3 exomes

AF:

0.259

AC:

64224

AN:

248048

Hom.:

9613

AF XY:

0.259

AC XY:

34773

AN XY:

134310

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.0664

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.281

AC:

410128

AN:

1457732

Hom.:

60779

Cov.:

AF XY:

0.280

AC XY:

202939

AN XY:

724932

show subpopulations

Gnomad4 AFR exome

AF:

0.482

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.0660

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.322

AC:

49003

AN:

152124

Hom.:

8709

Cov.:

AF XY:

0.316

AC XY:

23504

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.0740

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.248

Hom.:

1585

Bravo

AF:

0.324

EpiCase

AF:

0.297

EpiControl

AF:

0.290

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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

-0.86

CADD

Benign

0.59

DANN

Benign

0.64

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