6-35458325-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_021922.3(FANCE):c.998T>C(p.Leu333Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,976 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L333F) has been classified 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCE | NM_021922.3 | c.998T>C | p.Leu333Pro | missense_variant | 5/10 | ENST00000229769.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCE | ENST00000229769.3 | c.998T>C | p.Leu333Pro | missense_variant | 5/10 | 1 | NM_021922.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727212
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 07, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 333 of the FANCE protein (p.Leu333Pro). This variant is present in population databases (rs770592868, gnomAD 0.002%). 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: 539297). 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 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at