rs199422144
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018136.5(ASPM):c.1631_1635del(p.Tyr544SerfsTer9) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000527 in 1,612,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y544Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_018136.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.1631_1635del | p.Tyr544SerfsTer9 | frameshift_variant | 3/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.1631_1635del | p.Tyr544SerfsTer9 | frameshift_variant | 3/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.1631_1635del | p.Tyr544SerfsTer9 | frameshift_variant | 3/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152096Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250470Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135574
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1460184Hom.: 0 AF XY: 0.0000523 AC XY: 38AN XY: 726526
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152096Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74292
ClinVar
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles | Jan 01, 2020 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed multiple times with a pathogenic variant in unrelated patients referred for genetic testing at GeneDx and in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases (Passemard S et al., 2009); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19770472, 34402213) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at