8-143321315-GCG-CCT

Variant names:

• chr8-143321315-GCG-CCT
• NM_052963.3:c.1030_1032delCGCinsAGG
• TOP1MT p.345

Variant summary

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

The NM_052963.3(TOP1MT):​c.1030_1032delCGCinsAGG​(p.345) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R344R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TOP1MT NM_052963.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• Publications: 0 publications found

Genes affected

TOP1MT (HGNC:29787): (DNA topoisomerase I mitochondrial) This gene encodes a mitochondrial DNA topoisomerase that plays a role in the modification of DNA topology. The encoded protein is a type IB topoisomerase and catalyzes the transient breaking and rejoining of DNA to relieve tension and DNA supercoiling generated in the mitochondrial genome during replication and transcription. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052963.3. 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
	TOP1MT	NM_052963.3	MANE Select	c.1030_1032delCGCinsAGG	p.345	synonymous	N/A	NP_443195.1	Q969P6-1
	TOP1MT	NM_001258446.1		c.736_738delCGCinsAGG	p.247	synonymous	N/A	NP_001245375.1	Q969P6-2
	TOP1MT	NM_001258447.1		c.736_738delCGCinsAGG	p.247	synonymous	N/A	NP_001245376.1	Q969P6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP1MT	ENST00000329245.9	TSL:1 MANE Select	c.1030_1032delCGCinsAGG	p.345	synonymous	N/A	ENSP00000328835.3	Q969P6-1
	TOP1MT	ENST00000969804.1		c.1030_1032delCGCinsAGG	p.345	synonymous	N/A	ENSP00000639863.1
	TOP1MT	ENST00000870174.1		c.1030_1032delCGCinsAGG	p.345	synonymous	N/A	ENSP00000540233.1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

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: chr8-144403485;