rs565812419
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005751.5(AKAP9):c.3838-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,595,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005751.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.3838-4A>G | splice_region_variant, intron_variant | Intron 12 of 49 | ENST00000356239.8 | NP_005742.4 | ||
AKAP9 | NM_147185.3 | c.3838-4A>G | splice_region_variant, intron_variant | Intron 12 of 49 | NP_671714.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251304Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135830
GnomAD4 exome AF: 0.0000346 AC: 50AN: 1443802Hom.: 0 Cov.: 28 AF XY: 0.0000361 AC XY: 26AN XY: 719532
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Long QT syndrome 11 Uncertain:1
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Long QT syndrome Uncertain:1
This sequence change falls in intron 12 of the AKAP9 gene. It does not directly change the encoded amino acid sequence of the AKAP9 protein. This variant is present in population databases (rs565812419, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. ClinVar contains an entry for this variant (Variation ID: 939754). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
Cardiovascular phenotype Uncertain:1
The c.3838-4A>G intronic variant results from an A to G substitution 4 nucleotides upstream from coding exon 13 in the AKAP9 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at