rs767167128
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005751.5(AKAP9):āc.645A>Gā(p.Gln215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.000032 ( 0 hom. )
Consequence
AKAP9
NM_005751.5 synonymous
NM_005751.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.48
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 7-91994689-A-G is Benign according to our data. Variant chr7-91994689-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 240257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-91994689-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.48 with no splicing effect.
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.645A>G | p.Gln215= | synonymous_variant | 6/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.645A>G | p.Gln215= | synonymous_variant | 6/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.645A>G | p.Gln215= | synonymous_variant | 6/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000917 AC: 23AN: 250866Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135636
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461178Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726912
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
AKAP9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at