chr20-41084539-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_003286.4(TOP1):c.585G>A(p.Pro195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,571,722 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
TOP1
NM_003286.4 synonymous
NM_003286.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.776
Genes affected
TOP1 (HGNC:11986): (DNA topoisomerase I) 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 altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 20-41084539-G-A is Benign according to our data. Variant chr20-41084539-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035753.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.776 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOP1 | NM_003286.4 | c.585G>A | p.Pro195= | synonymous_variant | 8/21 | ENST00000361337.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOP1 | ENST00000361337.3 | c.585G>A | p.Pro195= | synonymous_variant | 8/21 | 1 | NM_003286.4 | P1 | |
TOP1 | ENST00000681058.1 | n.739G>A | non_coding_transcript_exon_variant | 8/20 | |||||
TOP1 | ENST00000681392.1 | n.1705G>A | non_coding_transcript_exon_variant | 4/18 | |||||
TOP1 | ENST00000681113.1 | c.585G>A | p.Pro195= | synonymous_variant, NMD_transcript_variant | 8/23 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152126Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000176 AC: 25AN: 1419596Hom.: 0 Cov.: 29 AF XY: 0.0000199 AC XY: 14AN XY: 702794
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TOP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at