rs151142538
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The ENST00000367409.9(ASPM):āc.9276T>Cā(p.Gly3092=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,610,864 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š 0.0010 ( 1 hom., cov: 32)
Exomes š: 0.000097 ( 0 hom. )
Consequence
ASPM
ENST00000367409.9 synonymous
ENST00000367409.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.760
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 -6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 1-197093070-A-G is Benign according to our data. Variant chr1-197093070-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 157907.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.76 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.001 (152/152074) while in subpopulation AFR AF= 0.00358 (149/41564). AF 95% confidence interval is 0.00312. There are 1 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.9276T>C | p.Gly3092= | synonymous_variant | 21/28 | ENST00000367409.9 | NP_060606.3 | |
ASPM | NM_001206846.2 | c.4521T>C | p.Gly1507= | synonymous_variant | 20/27 | NP_001193775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.9276T>C | p.Gly3092= | synonymous_variant | 21/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000994 AC: 151AN: 151956Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000260 AC: 65AN: 250000Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135108
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GnomAD4 exome AF: 0.0000973 AC: 142AN: 1458790Hom.: 0 Cov.: 31 AF XY: 0.0000841 AC XY: 61AN XY: 725746
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GnomAD4 genome AF: 0.00100 AC: 152AN: 152074Hom.: 1 Cov.: 32 AF XY: 0.00109 AC XY: 81AN XY: 74334
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 31, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 02, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 26, 2013 | - - |
ASPM-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 30, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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