12-66189430-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_007199.3(IRAK3):āc.131T>Cā(p.Leu44Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000238 in 1,300,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_007199.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRAK3 | NM_007199.3 | c.131T>C | p.Leu44Pro | missense_variant, splice_region_variant | 1/12 | ENST00000261233.9 | NP_009130.2 | |
IRAK3 | NM_001142523.2 | c.131T>C | p.Leu44Pro | missense_variant, splice_region_variant | 1/11 | NP_001135995.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IRAK3 | ENST00000261233.9 | c.131T>C | p.Leu44Pro | missense_variant, splice_region_variant | 1/12 | 1 | NM_007199.3 | ENSP00000261233.4 | ||
IRAK3 | ENST00000545837.1 | c.131T>C | p.Leu44Pro | missense_variant, splice_region_variant | 1/2 | 1 | ENSP00000441321.1 | |||
IRAK3 | ENST00000457197.2 | c.131T>C | p.Leu44Pro | missense_variant, splice_region_variant | 1/11 | 2 | ENSP00000409852.2 |
Frequencies
GnomAD3 genomes AF: 0.0000595 AC: 9AN: 151318Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000191 AC: 22AN: 1149636Hom.: 0 Cov.: 30 AF XY: 0.0000198 AC XY: 11AN XY: 554696
GnomAD4 genome AF: 0.0000595 AC: 9AN: 151318Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73880
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2024 | The c.131T>C (p.L44P) alteration is located in exon 1 (coding exon 1) of the IRAK3 gene. This alteration results from a T to C substitution at nucleotide position 131, causing the leucine (L) at amino acid position 44 to be replaced by a proline (P). 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