12-57472038-GAA-AAG

Variant names:

• chr12-57472038-GAA-AAG
• NM_005269.3:c.3298_3300delGAAinsAAG
• GLI1 p.Glu1100Lys

Variant summary

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

The NM_005269.3(GLI1):​c.3298_3300delGAAinsAAG​(p.Glu1100Lys) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E1100Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLI1 NM_005269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.28
• Publications: 0 publications found

Genes affected

GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ARHGAP9 (HGNC:14130): (Rho GTPase activating protein 9) This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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_005269.3. 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
	GLI1	NM_005269.3	MANE Select	c.3298_3300delGAAinsAAG	p.Glu1100Lys	missense	N/A	NP_005260.1	P08151-1
	GLI1	NM_001167609.2		c.3175_3177delGAAinsAAG	p.Glu1059Lys	missense	N/A	NP_001161081.1	P08151-2
	GLI1	NM_001160045.2		c.2914_2916delGAAinsAAG	p.Glu972Lys	missense	N/A	NP_001153517.1	P08151-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI1	ENST00000228682.7	TSL:1 MANE Select	c.3298_3300delGAAinsAAG	p.Glu1100Lys	missense	N/A	ENSP00000228682.2	P08151-1
	GLI1	ENST00000528467.1	TSL:1	c.3175_3177delGAAinsAAG	p.Glu1059Lys	missense	N/A	ENSP00000434408.1	P08151-2
	GLI1	ENST00000546141.5	TSL:5	c.3175_3177delGAAinsAAG	p.Glu1059Lys	missense	N/A	ENSP00000441006.1	P08151-2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

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: chr12-57865821;