Variant chr8-143331246-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_052963.3(TOP1MT):c.216C>T(p.Asp72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,609,386 control chromosomes in the GnomAD database, including 15,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 4186 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11498 hom. )

Consequence

TOP1MT
NM_052963.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-143331246-G-A is Benign according to our data. Variant chr8-143331246-G-A is described in ClinVar as [Benign]. Clinvar id is 1598715.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 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.216C>T	p.Asp72=	synonymous_variant	2/14	ENST00000329245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1MT	ENST00000329245.9 linkuse as main transcript	c.216C>T	p.Asp72=	synonymous_variant	2/14	1	NM_052963.3	P1	Q969P6-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29178

AN:

152024

Hom.:

4185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.0734

Gnomad SAS

AF:

0.0945

Gnomad FIN

AF:

0.0948

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.121

AC:

30274

AN:

250516

Hom.:

2683

AF XY:

0.115

AC XY:

15508

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.0755

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.0682

Gnomad SAS exome

AF:

0.0925

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.115

AC:

168208

AN:

1457244

Hom.:

11498

Cov.:

AF XY:

0.114

AC XY:

82451

AN XY:

724274

show subpopulations

Gnomad4 AFR exome

AF:

0.408

Gnomad4 AMR exome

AF:

0.0823

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.0757

Gnomad4 SAS exome

AF:

0.0913

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.192

AC:

29190

AN:

152142

Hom.:

4186

Cov.:

AF XY:

0.185

AC XY:

13755

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.0734

Gnomad4 SAS

AF:

0.0938

Gnomad4 FIN

AF:

0.0948

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.129

Hom.:

3179

Bravo

AF:

0.201

Asia WGS

AF:

0.107

AC:

372

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.110

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

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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