rs200250245
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005751.5(AKAP9):āc.1242C>Gā(p.Phe414Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. F414F) has been classified as Benign.
Frequency
Consequence
NM_005751.5 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 | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.1242C>G | p.Phe414Leu | missense_variant | 8/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.1242C>G | p.Phe414Leu | missense_variant | 8/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.1242C>G | p.Phe414Leu | missense_variant | 8/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151948Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250186Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135504
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727166
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151948Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 414 of the AKAP9 protein (p.Phe414Leu). This variant is present in population databases (no rsID available, gnomAD 0.008%). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 27, 2024 | The p.F414L variant (also known as c.1242C>G), located in coding exon 8 of the AKAP9 gene, results from a C to G substitution at nucleotide position 1242. The phenylalanine at codon 414 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at