rs745708169
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005751.5(AKAP9):āc.5456C>Gā(p.Thr1819Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,596 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 Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
AKAP9
NM_005751.5 missense
NM_005751.5 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 3.04
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.25327647).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.5456C>G | p.Thr1819Arg | missense_variant | 22/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.5456C>G | p.Thr1819Arg | missense_variant | 22/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.5456C>G | p.Thr1819Arg | missense_variant | 22/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251166Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135734
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461596Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727082
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
ExAC
?
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2017 | This sequence change replaces threonine with arginine at codon 1819 of the AKAP9 protein (p.Thr1819Arg). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs745708169, ExAC 0.009%). This variant has not been reported in the literature in individuals with AKAP9-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
T;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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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