NM_004618.5:c.*3435C>T
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004618.5(TOP3A):c.*3435C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,858 control chromosomes in the GnomAD database, including 7,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.31 ( 7413 hom., cov: 32)
Exomes 𝑓: 0.22 ( 27 hom. )
Consequence
TOP3A
NM_004618.5 downstream_gene
NM_004618.5 downstream_gene
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.327
Publications
11 publications found
Genes affected
TOP3A (HGNC:11992): (DNA topoisomerase III alpha) This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
TOP3A Gene-Disease associations (from GenCC):
- microcephaly, growth restriction, and increased sister chromatid exchange 2Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TOP3A | NM_004618.5 | c.*3435C>T | downstream_gene_variant | ENST00000321105.10 | NP_004609.1 | |||
TOP3A | NM_001320759.2 | c.*3435C>T | downstream_gene_variant | NP_001307688.1 | ||||
TOP3A | XM_047436633.1 | c.*3435C>T | downstream_gene_variant | XP_047292589.1 | ||||
TOP3A | XM_047436634.1 | c.*3435C>T | downstream_gene_variant | XP_047292590.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.305 AC: 46402AN: 151934Hom.: 7412 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
46402
AN:
151934
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.216 AC: 174AN: 806Hom.: 27 AF XY: 0.187 AC XY: 85AN XY: 454 show subpopulations
GnomAD4 exome
AF:
AC:
174
AN:
806
Hom.:
AF XY:
AC XY:
85
AN XY:
454
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AF:
AC:
6
AN:
58
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
6
East Asian (EAS)
AF:
AC:
0
AN:
6
South Asian (SAS)
AF:
AC:
29
AN:
198
European-Finnish (FIN)
AF:
AC:
8
AN:
44
Middle Eastern (MID)
AF:
AC:
0
AN:
4
European-Non Finnish (NFE)
AF:
AC:
123
AN:
452
Other (OTH)
AF:
AC:
6
AN:
38
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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: 0.305 AC: 46439AN: 152052Hom.: 7413 Cov.: 32 AF XY: 0.301 AC XY: 22364AN XY: 74324 show subpopulations
GnomAD4 genome
AF:
AC:
46439
AN:
152052
Hom.:
Cov.:
32
AF XY:
AC XY:
22364
AN XY:
74324
show subpopulations
African (AFR)
AF:
AC:
14358
AN:
41452
American (AMR)
AF:
AC:
3791
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
1138
AN:
3472
East Asian (EAS)
AF:
AC:
390
AN:
5182
South Asian (SAS)
AF:
AC:
898
AN:
4818
European-Finnish (FIN)
AF:
AC:
3423
AN:
10560
Middle Eastern (MID)
AF:
AC:
87
AN:
294
European-Non Finnish (NFE)
AF:
AC:
21455
AN:
67974
Other (OTH)
AF:
AC:
609
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1606
3211
4817
6422
8028
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
470
940
1410
1880
2350
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
531
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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