15-89260839-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001113378.2(FANCI):c.284T>A(p.Leu95Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,736 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L95P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001113378.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.284T>A | p.Leu95Gln | missense_variant | 4/38 | ENST00000310775.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.284T>A | p.Leu95Gln | missense_variant | 4/38 | 1 | NM_001113378.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251452Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135894
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461420Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8AN XY: 727024
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74478
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 95 of the FANCI protein (p.Leu95Gln). This variant is present in population databases (rs201553891, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 456211). 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 FANCI protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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