Variant 8-143321279-G-A 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.1068C>T(p.Gly356Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,194 control chromosomes in the GnomAD database, including 9,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1379 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8253 hom. )

Consequence

TOP1MT
NM_052963.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.450

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=-0.81).

BP6

Variant 8-143321279-G-A is Benign according to our data. Variant chr8-143321279-G-A is described in ClinVar as [Benign]. Clinvar id is 1529061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP1MT	NM_052963.3 linkuse as main transcript	c.1068C>T	p.Gly356Gly	synonymous_variant	8/14	ENST00000329245.9	NP_443195.1	Q969P6-1E5KMK7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP1MT	ENST00000329245.9 linkuse as main transcript	c.1068C>T	p.Gly356Gly	synonymous_variant	8/14	1	NM_052963.3	ENSP00000328835.3		Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19062

AN:

152128

Hom.:

1381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.0737

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.0959

AC:

23873

AN:

249040

Hom.:

1348

AF XY:

0.0939

AC XY:

12658

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.0656

Gnomad SAS exome

AF:

0.0742

Gnomad FIN exome

AF:

0.0715

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0969

GnomAD4 exome

AF:

0.103

AC:

150286

AN:

1459948

Hom.:

8253

Cov.:

AF XY:

0.102

AC XY:

73922

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.0652

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0805

Gnomad4 SAS exome

AF:

0.0731

Gnomad4 FIN exome

AF:

0.0712

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.125

AC:

19077

AN:

152246

Hom.:

1379

Cov.:

AF XY:

0.123

AC XY:

9127

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.0847

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.0749

Gnomad4 SAS

AF:

0.0737

Gnomad4 FIN

AF:

0.0708

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.118

Hom.:

573

Bravo

AF:

0.128

Asia WGS

AF:

0.0920

AC:

320

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	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

-0.81

CADD

Benign

1.4

DANN

Benign

0.56

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