5-170106100-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012188.5(FOXI1):c.143C>T(p.Ser48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012188.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXI1 | NM_012188.5 | c.143C>T | p.Ser48Phe | missense_variant | Exon 1 of 2 | ENST00000306268.8 | NP_036320.2 | |
FOXI1 | NM_144769.4 | c.143C>T | p.Ser48Phe | missense_variant | Exon 1 of 2 | NP_658982.1 | ||
FOXI1 | XR_941092.2 | n.204C>T | non_coding_transcript_exon_variant | Exon 1 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461032Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726772
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 48 of the FOXI1 protein (p.Ser48Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FOXI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1464208). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FOXI1 protein function with a positive predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at