rs749111562
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021922.3(FANCE):c.856-3C>T 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 0.00000684 in 1,461,540 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 predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_021922.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCE | NM_021922.3 | c.856-3C>T | 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.856-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_021922.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250578Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135498
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461540Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727078
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia complementation group E Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 31, 2022 | ClinVar contains an entry for this variant (Variation ID: 471932). This sequence change falls in intron 2 of the FANCE gene. It does not directly change the encoded amino acid sequence of the FANCE protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs749111562, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | May 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at