rs74162087
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_022168.4(IFIH1):c.2459G>T(p.Arg820Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R820H) has been classified as Uncertain significance.
Frequency
Consequence
NM_022168.4 missense
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 | UniProt |
---|---|---|---|---|---|---|---|
IFIH1 | NM_022168.4 | c.2459G>T | p.Arg820Leu | missense_variant | 13/16 | ENST00000649979.2 | |
IFIH1 | XM_047445407.1 | c.1742G>T | p.Arg581Leu | missense_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFIH1 | ENST00000649979.2 | c.2459G>T | p.Arg820Leu | missense_variant | 13/16 | NM_022168.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459302Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725950
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 7;C4225427:Singleton-Merten syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 820 of the IFIH1 protein (p.Arg820Leu). This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at