1-197091956-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_018136.5(ASPM):āc.9395T>Cā(p.Leu3132Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,611,584 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3132R) has been classified as Benign.
Frequency
Consequence
NM_018136.5 missense
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.9395T>C | p.Leu3132Pro | missense_variant | 22/28 | ENST00000367409.9 | NP_060606.3 | |
ASPM | NM_001206846.2 | c.4640T>C | p.Leu1547Pro | missense_variant | 21/27 | NP_001193775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.9395T>C | p.Leu3132Pro | missense_variant | 22/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250620Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135436
GnomAD4 exome AF: 0.0000767 AC: 112AN: 1459462Hom.: 0 Cov.: 31 AF XY: 0.0000840 AC XY: 61AN XY: 726092
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74392
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 11, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 25, 2021 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3132 of the ASPM protein (p.Leu3132Pro). This variant is present in population databases (rs36004306, gnomAD 0.02%). This missense change has been observed in individual(s) with primary microcephaly, however a second variant was not identified (PMID: 23611254). ClinVar contains an entry for this variant (Variation ID: 157911). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Microcephaly 5, primary, autosomal recessive Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at