12-66196952-AC-GT

Variant names:

• chr12-66196952-AC-GT
• ENST00000545837.1:c.206_207delACinsGT
• IRAK3 p.Tyr69Cys

Variant summary

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

The ENST00000545837.1(IRAK3):​c.206_207delACinsGT​(p.Tyr69Cys) variant causes a missense change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAK3 ENST00000545837.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

IRAK3 (HGNC:17020): (interleukin 1 receptor associated kinase 3) This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to asthma. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

IRAK3 Gene-Disease associations (from GenCC):

• asthma-related traits, susceptibility to, 5

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545837.1. 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
	IRAK3	NM_007199.3	MANE Select	c.134-6759_134-6758delACinsGT		intron	N/A	NP_009130.2	Q9Y616-1
	IRAK3	NM_001142523.2		c.133+7520_133+7521delACinsGT		intron	N/A	NP_001135995.1	Q9Y616-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK3	ENST00000545837.1	TSL:1	c.206_207delACinsGT	p.Tyr69Cys	missense	N/A	ENSP00000441321.1	F5GYN6
	IRAK3	ENST00000261233.9	TSL:1 MANE Select	c.134-6759_134-6758delACinsGT		intron	N/A	ENSP00000261233.4	Q9Y616-1
	IRAK3	ENST00000854785.1		c.134-6762_134-6761delACinsGT		intron	N/A	ENSP00000524844.1

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		1.8

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: chr12-66590732;