chr20-41077586-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_003286.4(TOP1):c.284G>A(p.Arg95Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003286.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOP1 | NM_003286.4 | c.284G>A | p.Arg95Gln | missense_variant | 5/21 | ENST00000361337.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOP1 | ENST00000361337.3 | c.284G>A | p.Arg95Gln | missense_variant | 5/21 | 1 | NM_003286.4 | P1 | |
TOP1 | ENST00000681058.1 | n.438G>A | non_coding_transcript_exon_variant | 5/20 | |||||
TOP1 | ENST00000681392.1 | n.1404G>A | non_coding_transcript_exon_variant | 1/18 | |||||
TOP1 | ENST00000681113.1 | c.284G>A | p.Arg95Gln | missense_variant, NMD_transcript_variant | 5/23 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251260Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135782
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461680Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727160
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2022 | The c.284G>A (p.R95Q) alteration is located in exon 5 (coding exon 5) of the TOP1 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at