rs369801034
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_018136.5(ASPM):c.81C>A(p.Pro27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,610,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
ASPM
NM_018136.5 synonymous
NM_018136.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.05
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-197146357-G-T is Benign according to our data. Variant chr1-197146357-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 157889.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr1-197146357-G-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.05 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ASPM | NM_018136.5 | c.81C>A | p.Pro27= | synonymous_variant | 1/28 | ENST00000367409.9 | NP_060606.3 | |
| ASPM | NM_001206846.2 | c.81C>A | p.Pro27= | synonymous_variant | 1/27 | NP_001193775.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ASPM | ENST00000367409.9 | c.81C>A | p.Pro27= | synonymous_variant | 1/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 |
Frequencies
GnomAD3 genomes 0.000178 AC: 27AN: 151888Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000237 AC: 56AN: 236314Hom.: 0 AF XY: 0.000261 AC XY: 34AN XY: 130408
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GnomAD4 exome AF: 0.000248 AC: 362AN: 1458886Hom.: 0 Cov.: 31 AF XY: 0.000258 AC XY: 187AN XY: 725628
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GnomAD4 genome 0.000178 AC: 27AN: 151998Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10AN XY: 74266
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2023 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | ASPM: BP4, BP7 - |
Microcephaly 5, primary, autosomal recessive Uncertain:1
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
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BayesDel_noAF
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at