dbSNP rs188200124: TOP1MT:p.Ala535Ala (chr8-143310166-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_052963.3(TOP1MT):c.1605G>A(p.Ala535Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000815 in 1,607,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

TOP1MT
NM_052963.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.686

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.025).

BP6

Variant 8-143310166-C-T is Benign according to our data. Variant chr8-143310166-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2170208.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.686 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052963.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOP1MT	NM_052963.3	MANE Select	c.1605G>A	p.Ala535Ala	synonymous	Exon 13 of 14	NP_443195.1	Q969P6-1
TOP1MT	NM_001258446.1		c.1311G>A	p.Ala437Ala	synonymous	Exon 14 of 15	NP_001245375.1	Q969P6-2
TOP1MT	NM_001258447.1		c.1311G>A	p.Ala437Ala	synonymous	Exon 13 of 14	NP_001245376.1	Q969P6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOP1MT	ENST00000329245.9	TSL:1 MANE Select	c.1605G>A	p.Ala535Ala	synonymous	Exon 13 of 14	ENSP00000328835.3	Q969P6-1
TOP1MT	ENST00000969804.1		c.1695G>A	p.Ala565Ala	synonymous	Exon 13 of 14	ENSP00000639863.1
TOP1MT	ENST00000870174.1		c.1605G>A	p.Ala535Ala	synonymous	Exon 13 of 14	ENSP00000540233.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000120

AC:

AN:

241396

AF XY:

0.000137

show subpopulations

Gnomad AFR exome

AF:

0.000193

Gnomad AMR exome

AF:

0.0000901

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000756

AC:

110

AN:

1454944

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

723466

show subpopulations

African (AFR)

AF:

0.000301

AC:

AN:

33240

American (AMR)

AF:

0.0000456

AC:

AN:

43862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25756

East Asian (EAS)

AF:

0.000278

AC:

AN:

39608

South Asian (SAS)

AF:

0.000397

AC:

AN:

85668

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52244

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1108964

Other (OTH)

AF:

0.000517

AC:

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41578

American (AMR)

AF:

0.000457

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000174

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.0

(source)

DANN

Benign

0.84

PhyloP100

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over