Variant 8-143309468-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_052963.3(TOP1MT):c.1779C>T(p.Ala593=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00257 in 1,613,924 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 35 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 40 hom. )

Consequence

TOP1MT
NM_052963.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.85

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-143309468-G-A is Benign according to our data. Variant chr8-143309468-G-A is described in ClinVar as [Benign]. Clinvar id is 1633361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1661/152306) while in subpopulation AFR AF= 0.036 (1497/41550). AF 95% confidence interval is 0.0345. There are 35 homozygotes in gnomad4. There are 791 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOP1MT	NM_052963.3 linkuse as main transcript	c.1779C>T	p.Ala593=	synonymous_variant	14/14	ENST00000329245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1MT	ENST00000329245.9 linkuse as main transcript	c.1779C>T	p.Ala593=	synonymous_variant	14/14	1	NM_052963.3	P1	Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1647

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00340

AC:

853

AN:

251162

Hom.:

AF XY:

0.00271

AC XY:

368

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000492

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00170

AC:

2492

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1119

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0381

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.0109

AC:

1661

AN:

152306

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

791

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000711

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	Jan 06, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.5

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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