chr1-197086804-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018136.5(ASPM):āc.10330A>Cā(p.Arg3444=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000873 in 1,604,530 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 (ā ).
Frequency
Consequence
NM_018136.5 splice_region, synonymous
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 |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.10330A>C | p.Arg3444= | splice_region_variant, synonymous_variant | 27/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.5575A>C | p.Arg1859= | splice_region_variant, synonymous_variant | 26/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.10330A>C | p.Arg3444= | splice_region_variant, synonymous_variant | 27/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452188Hom.: 0 Cov.: 32 AF XY: 0.00000553 AC XY: 4AN XY: 723084
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2021 | This variant has not been reported in the literature in individuals with ASPM-related conditions. This variant is present in population databases (rs140231146, ExAC 0.01%). This sequence change affects codon 3444 of the ASPM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ASPM protein. It affects a nucleotide within the consensus splice site of the intron. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at