1-24964518-GAT-AGA

Variant names:

• chr1-24964518-GAT-AGA
• ENST00000338888.4:c.52_54delATCinsTCT
• RUNX3 p.Ile18Ser

Variant summary

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

The NM_001031680.2(RUNX3):​c.52_54delATCinsTCT​(p.Ile18Ser) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I18N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX3 NM_001031680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

RUNX3 (HGNC:10473): (RUNX family transcription factor 3) This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-PYGPYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

RUNX3-AS1 (HGNC:40513): (RUNX3 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031680.2. 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
	RUNX3	NM_001031680.2		c.52_54delATCinsTCT	p.Ile18Ser	missense	N/A	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.52_54delATCinsTCT	p.Ile18Ser	missense	N/A	NP_001307601.1	Q13761-2
	RUNX3-AS1	NR_183339.1		n.3837_3839delGATinsAGA		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.52_54delATCinsTCT	p.Ile18Ser	missense	N/A	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000479341.1	TSL:1	n.162_164delATCinsTCT		non_coding_transcript_exon	Exon 2 of 3
	RUNX3	ENST00000399916.5	TSL:2	c.52_54delATCinsTCT	p.Ile18Ser	missense	N/A	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

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: chr1-25291009;