14-24162251-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006084.5(IRF9):c.107C>T(p.Thr36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T36T) has been classified as Benign.
Frequency
Consequence
NM_006084.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRF9 | NM_006084.5 | c.107C>T | p.Thr36Ile | missense_variant | Exon 2 of 9 | ENST00000396864.8 | NP_006075.3 | |
IRF9 | NM_001385400.1 | c.107C>T | p.Thr36Ile | missense_variant | Exon 2 of 10 | NP_001372329.1 | ||
IRF9 | NM_001385401.1 | c.107C>T | p.Thr36Ile | missense_variant | Exon 2 of 9 | NP_001372330.1 | ||
IRF9 | NM_001385402.1 | c.107C>T | p.Thr36Ile | missense_variant | Exon 2 of 9 | NP_001372331.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IRF9 | ENST00000396864.8 | c.107C>T | p.Thr36Ile | missense_variant | Exon 2 of 9 | 1 | NM_006084.5 | ENSP00000380073.3 | ||
ENSG00000259529 | ENST00000558468.2 | n.*873C>T | non_coding_transcript_exon_variant | Exon 22 of 29 | 2 | ENSP00000457512.2 | ||||
ENSG00000259529 | ENST00000558468.2 | n.*873C>T | 3_prime_UTR_variant | Exon 22 of 29 | 2 | ENSP00000457512.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1472545). This variant has not been reported in the literature in individuals affected with IRF9-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 36 of the IRF9 protein (p.Thr36Ile). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.