chr2-162277463-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_022168.4(IFIH1):c.1996C>G(p.Pro666Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. P666S) has been classified as Likely benign.
Frequency
Consequence
NM_022168.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFIH1 | NM_022168.4 | c.1996C>G | p.Pro666Ala | missense_variant | 10/16 | ENST00000649979.2 | |
IFIH1 | XM_047445407.1 | c.1279C>G | p.Pro427Ala | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFIH1 | ENST00000649979.2 | c.1996C>G | p.Pro666Ala | missense_variant | 10/16 | NM_022168.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244328Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132060
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456498Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 724458
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 | Jun 28, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. This variant is present in population databases (rs376074455, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 666 of the IFIH1 protein (p.Pro666Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at