12-66189304-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_007199.3(IRAK3):āc.5C>Gā(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000716 in 1,536,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2E) has been classified as Uncertain significance.
Frequency
Consequence
NM_007199.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRAK3 | NM_007199.3 | c.5C>G | p.Ala2Gly | missense_variant | 1/12 | ENST00000261233.9 | |
IRAK3 | NM_001142523.2 | c.5C>G | p.Ala2Gly | missense_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRAK3 | ENST00000261233.9 | c.5C>G | p.Ala2Gly | missense_variant | 1/12 | 1 | NM_007199.3 | P1 | |
IRAK3 | ENST00000545837.1 | c.5C>G | p.Ala2Gly | missense_variant | 1/2 | 1 | |||
IRAK3 | ENST00000457197.2 | c.5C>G | p.Ala2Gly | missense_variant | 1/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152192Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000289 AC: 4AN: 1383824Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 683098
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74480
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.5C>G (p.A2G) alteration is located in exon 1 (coding exon 1) of the IRAK3 gene. This alteration results from a C to G substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at