rs1287242303
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000229769.3(FANCE):c.679G>A(p.Glu227Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000229769.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCE | NM_021922.3 | c.679G>A | p.Glu227Lys | missense_variant | 2/10 | ENST00000229769.3 | NP_068741.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCE | ENST00000229769.3 | c.679G>A | p.Glu227Lys | missense_variant | 2/10 | 1 | NM_021922.3 | ENSP00000229769 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 Cov.: 39 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 2021 | This sequence change replaces glutamic acid with lysine at codon 227 of the FANCE protein (p.Glu227Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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