rs375059809
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000367409.9(ASPM):c.2312G>A(p.Arg771His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000367409.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.2312G>A | p.Arg771His | missense_variant | 6/28 | ENST00000367409.9 | NP_060606.3 | |
ASPM | NM_001206846.2 | c.2312G>A | p.Arg771His | missense_variant | 6/27 | NP_001193775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.2312G>A | p.Arg771His | missense_variant | 6/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251322Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727190
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 11, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 10, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 20, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 771 of the ASPM protein (p.Arg771His). This variant is present in population databases (rs375059809, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ASPM-related conditions. ClinVar contains an entry for this variant (Variation ID: 434411). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at