rs758465541
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_014679.5(CEP57):c.1273C>T(p.Leu425=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,605,188 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_014679.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP57 | NM_014679.5 | c.1273C>T | p.Leu425= | splice_region_variant, synonymous_variant | 11/11 | ENST00000325542.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP57 | ENST00000325542.10 | c.1273C>T | p.Leu425= | splice_region_variant, synonymous_variant | 11/11 | 1 | NM_014679.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151864Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250550Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135666
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453324Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 723524
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151864Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74164
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2021 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CEP57-related disease. This variant is present in population databases (rs758465541, ExAC 0.002%). This sequence change affects codon 425 of the CEP57 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CEP57 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at