19-17762759-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015122.3(FCHO1):c.28-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015122.3 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FCHO1 | ENST00000596536.6 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | 5 | NM_015122.3 | ENSP00000470731.1 | |||
FCHO1 | ENST00000699212.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 29 | ENSP00000514208.1 | |||||
FCHO1 | ENST00000594202.6 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | 5 | ENSP00000473001.1 | ||||
FCHO1 | ENST00000596309.6 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | 4 | ENSP00000470511.2 | ||||
FCHO1 | ENST00000596951.6 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | 5 | ENSP00000472417.1 | ||||
FCHO1 | ENST00000600209.6 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | 5 | ENSP00000469075.2 | ||||
FCHO1 | ENST00000600676.5 | c.28-3C>A | splice_region_variant, intron_variant | Intron 3 of 27 | 2 | ENSP00000470493.1 | ||||
FCHO1 | ENST00000699176.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514179.1 | |||||
FCHO1 | ENST00000699177.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514180.1 | |||||
FCHO1 | ENST00000699207.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514204.1 | |||||
FCHO1 | ENST00000699209.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514206.1 | |||||
FCHO1 | ENST00000699215.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 3 of 27 | ENSP00000514211.1 | |||||
FCHO1 | ENST00000699202.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514200.1 | |||||
FCHO1 | ENST00000699214.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 3 of 27 | ENSP00000514210.1 | |||||
FCHO1 | ENST00000699208.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 27 | ENSP00000514205.1 | |||||
FCHO1 | ENST00000699198.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514196.1 | |||||
FCHO1 | ENST00000699199.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 3 of 27 | ENSP00000514197.1 | |||||
FCHO1 | ENST00000699213.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 3 of 27 | ENSP00000514209.1 | |||||
FCHO1 | ENST00000699197.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 27 | ENSP00000514195.1 | |||||
FCHO1 | ENST00000699200.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 27 | ENSP00000514198.1 | |||||
FCHO1 | ENST00000699196.1 | c.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 26 | ENSP00000514194.1 | |||||
FCHO1 | ENST00000699203.1 | c.-123-3C>A | splice_region_variant, intron_variant | Intron 2 of 21 | ENSP00000514201.1 | |||||
FCHO1 | ENST00000699201.1 | n.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 27 | ENSP00000514199.1 | |||||
FCHO1 | ENST00000699205.1 | n.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 26 | ENSP00000514202.1 | |||||
FCHO1 | ENST00000699206.1 | n.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 28 | ENSP00000514203.1 | |||||
FCHO1 | ENST00000699210.1 | n.28-3C>A | splice_region_variant, intron_variant | Intron 4 of 27 | ENSP00000514207.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with FCHO1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the FCHO1 gene. It does not directly change the encoded amino acid sequence of the FCHO1 protein. It affects a nucleotide within the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1499707). 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. 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 is not likely to affect RNA splicing. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at