TOPBP1 p.Leu1360Leu

Variant names:

• chr3-133611096-T-T
• NM_007027.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-133611097--
• chr3-133611099-G-A
• chr3-133611097-C-A
• chr3-133611097-C-G
• chr3-133611097-C-T
• chr3-133611097-CAG-TAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007027.4(TOPBP1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPBP1 NM_007027.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

Genes affected

TOPBP1 (HGNC:17008): (DNA topoisomerase II binding protein 1) This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands. [provided by RefSeq, Jul 2008]

TOPBP1 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPBP1	NM_007027.4	MANE Select	c.		exon_region	Exon 25 of 28	NP_008958.2	Q92547
	TOPBP1	NM_001363889.2		c.		exon_region	Exon 25 of 28	NP_001350818.1	A0A2R8YD63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPBP1	ENST00000260810.10	TSL:1 MANE Select	c.		exon_region	Exon 25 of 28	ENSP00000260810.5	Q92547
	TOPBP1	ENST00000881661.1		c.		exon_region	Exon 25 of 28	ENSP00000551720.1
	TOPBP1	ENST00000953681.1		c.		exon_region	Exon 25 of 28	ENSP00000623740.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-133329940;