rs9785013
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000356239.8(AKAP9):c.5163-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,570,554 control chromosomes in the GnomAD database, including 128,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.45 ( 16898 hom., cov: 32)
Exomes 𝑓: 0.39 ( 111868 hom. )
Consequence
AKAP9
ENST00000356239.8 intron
ENST00000356239.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.431
Genes affected
AKAP9 (HGNC:379): (A-kinase anchoring protein 9) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternate splicing of this gene results in at least two isoforms that localize to the centrosome and the Golgi apparatus, and interact with numerous signaling proteins from multiple signal transduction pathways. These signaling proteins include type II protein kinase A, serine/threonine kinase protein kinase N, protein phosphatase 1, protein phosphatase 2a, protein kinase C-epsilon and phosphodiesterase 4D3. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 7-92044988-G-A is Benign according to our data. Variant chr7-92044988-G-A is described in ClinVar as [Benign]. Clinvar id is 136331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92044988-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.5163-20G>A | intron_variant | ENST00000356239.8 | NP_005742.4 | |||
AKAP9 | NM_147185.3 | c.5163-20G>A | intron_variant | NP_671714.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.5163-20G>A | intron_variant | 1 | NM_005751.5 | ENSP00000348573 | P4 |
Frequencies
GnomAD3 genomes AF: 0.454 AC: 68922AN: 151872Hom.: 16861 Cov.: 32
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GnomAD3 exomes AF: 0.391 AC: 97948AN: 250218Hom.: 20351 AF XY: 0.391 AC XY: 52930AN XY: 135374
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GnomAD4 exome AF: 0.392 AC: 556095AN: 1418564Hom.: 111868 Cov.: 27 AF XY: 0.392 AC XY: 277698AN XY: 708534
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GnomAD4 genome AF: 0.454 AC: 69017AN: 151990Hom.: 16898 Cov.: 32 AF XY: 0.451 AC XY: 33511AN XY: 74270
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 12, 2019 | Variant summary: AKAP9 c.5163-20G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.39 in 250218 control chromosomes, predominantly at a frequency of 0.65 within the African or African-American subpopulation in the gnomAD database, including 3362 homozygotes. Therefore, suggesting the variant is the major allele observed in population(s) of African-American origin. A ClinVar submission (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 08, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2011 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Long QT syndrome 11 Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Long QT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at