chr1-197105037-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018136.5(ASPM):āc.4214G>Cā(p.Arg1405Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,610,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1405C) has been classified as Likely benign.
Frequency
Consequence
NM_018136.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.4214G>C | p.Arg1405Pro | missense_variant | 18/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.4066-8873G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.4214G>C | p.Arg1405Pro | missense_variant | 18/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151824Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249522Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134950
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458418Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725180
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151824Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74128
ClinVar
Submissions by phenotype
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at