8-91970694-TGC-AGT

Variant names:

• chr8-91970694-TGC-AGT
• NM_175634.3:c.1501_1503delGCAinsACT
• RUNX1T1 p.Ala501Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_175634.3(RUNX1T1):​c.1501_1503delGCAinsACT​(p.Ala501Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX1T1 NM_175634.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.16
• Publications: 0 publications found

Genes affected

RUNX1T1 (HGNC:1535): (RUNX1 partner transcriptional co-repressor 1) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

RUNX1T1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175634.3. 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
	RUNX1T1	NM_175634.3	MANE Select	c.1501_1503delGCAinsACT	p.Ala501Thr	missense	N/A	NP_783552.1	Q06455-1
	RUNX1T1	NM_001198679.3		c.1678_1680delGCAinsACT	p.Ala560Thr	missense	N/A	NP_001185608.1	A0A0A0MSU1
	RUNX1T1	NM_001395209.1		c.1585_1587delGCAinsACT	p.Ala529Thr	missense	N/A	NP_001382138.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1T1	ENST00000523629.7	TSL:5 MANE Select	c.1501_1503delGCAinsACT	p.Ala501Thr	missense	N/A	ENSP00000428543.1	Q06455-1
	RUNX1T1	ENST00000396218.5	TSL:1	c.1420_1422delGCAinsACT	p.Ala474Thr	missense	N/A	ENSP00000379520.1	Q06455-2
	RUNX1T1	ENST00000518844.5	TSL:1	c.1420_1422delGCAinsACT	p.Ala474Thr	missense	N/A	ENSP00000430728.1	Q06455-2

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		8.2

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: chr8-92982922;