6-393205-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002460.4(IRF4):c.53G>C(p.Ser18Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,559,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S18N) has been classified as Uncertain significance.
Frequency
Consequence
NM_002460.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF4 | NM_002460.4 | c.53G>C | p.Ser18Thr | missense_variant | 2/9 | ENST00000380956.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF4 | ENST00000380956.9 | c.53G>C | p.Ser18Thr | missense_variant | 2/9 | 1 | NM_002460.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000377 AC: 53AN: 1407048Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 19AN XY: 694884
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2023 | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 18 of the IRF4 protein (p.Ser18Thr). This variant has not been reported in the literature in individuals affected with IRF4-related conditions. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at