rs12677
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_018136.5(ASPM):c.*81C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,029,454 control chromosomes in the GnomAD database, including 408,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.78 ( 49995 hom., cov: 30)
Exomes 𝑓: 0.90 ( 358008 hom. )
Consequence
ASPM
NM_018136.5 3_prime_UTR
NM_018136.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.02
Genes affected
ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 1-197084243-G-A is Benign according to our data. Variant chr1-197084243-G-A is described in ClinVar as [Benign]. Clinvar id is 294591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.*81C>T | 3_prime_UTR_variant | 28/28 | ENST00000367409.9 | ||
ASPM | NM_001206846.2 | c.*81C>T | 3_prime_UTR_variant | 27/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.*81C>T | 3_prime_UTR_variant | 28/28 | 1 | NM_018136.5 | P1 | ||
ASPM | ENST00000294732.11 | c.*81C>T | 3_prime_UTR_variant | 27/27 | 1 | ||||
ASPM | ENST00000367408.6 | n.3802C>T | non_coding_transcript_exon_variant | 18/18 | 1 | ||||
ASPM | ENST00000680265.1 | c.*81C>T | 3_prime_UTR_variant | 29/29 |
Frequencies
GnomAD3 genomes ? AF: 0.784 AC: 119167AN: 151916Hom.: 49972 Cov.: 30
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GnomAD4 exome AF: 0.900 AC: 789604AN: 877420Hom.: 358008 Cov.: 11 AF XY: 0.901 AC XY: 412116AN XY: 457274
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GnomAD4 genome ? AF: 0.784 AC: 119240AN: 152034Hom.: 49995 Cov.: 30 AF XY: 0.789 AC XY: 58643AN XY: 74316
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at