rs878854342
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong
The NM_021922.3(FANCE):c.1114-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_021922.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCE | NM_021922.3 | c.1114-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000229769.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCE | ENST00000229769.3 | c.1114-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_021922.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151874Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727194
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151874Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74146
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Pathogenic:4Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 22, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change falls in intron 5 of the FANCE gene. It does not directly change the encoded amino acid sequence of the FANCE protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with Fanconi anemia (PMID: 10205272, 35295078; Invitae). ClinVar contains an entry for this variant (Variation ID: 8711). Studies have shown that this variant results in activation of cryptic splice site and introduces a premature termination codon (PMID: 11001585). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2000 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 28, 2023 | - - |
Uncertain significance, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 07, 2011 | Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | FANCE: PM2, PM3:Supporting, PP3, PS3:Supporting, PS4:Supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at