rs142746353
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000229769.3(FANCE):c.559G>A(p.Glu187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E187E) has been classified as Likely benign.
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.559G>A | p.Glu187Lys | 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.559G>A | p.Glu187Lys | missense_variant | 2/10 | 1 | NM_021922.3 | ENSP00000229769 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000523 AC: 13AN: 248646Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134766
GnomAD4 exome AF: 0.0000938 AC: 137AN: 1461228Hom.: 0 Cov.: 40 AF XY: 0.0000853 AC XY: 62AN XY: 726864
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74322
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2021 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 187 of the FANCE protein (p.Glu187Lys). This variant is present in population databases (rs142746353, gnomAD 0.01%). 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: 539299). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at