15-89293045-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001113378.2(FANCI):āc.2273T>Gā(p.Phe758Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,406 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. F758F) has been classified as Likely benign.
Frequency
Consequence
NM_001113378.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.2273T>G | p.Phe758Cys | missense_variant | 22/38 | ENST00000310775.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.2273T>G | p.Phe758Cys | missense_variant | 22/38 | 1 | NM_001113378.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251024Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135724
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461406Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727030
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces phenylalanine with cysteine at codon 758 of the FANCI protein (p.Phe758Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is present in population databases (rs750735931, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. 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. 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