rs147390386
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021922.3(FANCE):c.1591T>A(p.Leu531Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,070 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
NM_021922.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251486Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135920
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460858Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726804
GnomAD4 genome AF: 0.000171 AC: 26AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74354
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Uncertain:2
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This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 531 of the FANCE protein (p.Leu531Met). This variant is present in population databases (rs147390386, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 471923). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FANCE 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. -
FANCE-related disorder Uncertain:1
The FANCE c.1591T>A variant is predicted to result in the amino acid substitution p.Leu531Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.064% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-35434102-T-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at