rs762149925

Variant names:

• chr17-18274985-C-A
• rs762149925
• NM_004618.5:c.2828-5G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-18274985-C-A
• chr17-18274985-C-G
• chr17-18274985-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004618.5(TOP3A):​c.2828-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TOP3A NM_004618.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002387
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP3A	NM_004618.5	c.2828-5G>T		splice_region_variant, intron_variant	Intron 18 of 18	ENST00000321105.10	NP_004609.1
TOP3A	NM_001320759.2	c.2543-5G>T		splice_region_variant, intron_variant	Intron 17 of 17		NP_001307688.1
TOP3A	XM_047436633.1	c.1907-5G>T		splice_region_variant, intron_variant	Intron 16 of 16		XP_047292589.1
TOP3A	XM_047436634.1	c.1907-5G>T		splice_region_variant, intron_variant	Intron 16 of 16		XP_047292590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOP3A	ENST00000321105.10	c.2828-5G>T		splice_region_variant, intron_variant	Intron 18 of 18	1	NM_004618.5	ENSP00000321636.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460570 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs762149925; hg19: chr17-18178299;