rs755403672
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001113378.2(FANCI):āc.3255T>Gā(p.Cys1085Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000986 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001113378.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.3255T>G | p.Cys1085Trp | missense_variant, splice_region_variant | 30/38 | ENST00000310775.12 | NP_001106849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.3255T>G | p.Cys1085Trp | missense_variant, splice_region_variant | 30/38 | 1 | NM_001113378.2 | ENSP00000310842 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000837 AC: 21AN: 251020Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135808
GnomAD4 exome AF: 0.000102 AC: 149AN: 1461092Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 726856
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 1085 of the FANCI protein (p.Cys1085Trp). This variant is present in population databases (rs755403672, gnomAD 0.02%). 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: 568595). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Fanconi anemia complementation group I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 26, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at