rs148920964
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_005751.5(AKAP9):c.610G>A(p.Asp204Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,613,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )
Consequence
AKAP9
NM_005751.5 missense
NM_005751.5 missense
Scores
4
3
9
Clinical Significance
Conservation
PhyloP100: 9.24
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.019530147).
BP6
?
Variant 7-91994654-G-A is Benign according to our data. Variant chr7-91994654-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 190513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-91994654-G-A is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.610G>A | p.Asp204Asn | missense_variant | 6/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.610G>A | p.Asp204Asn | missense_variant | 6/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.610G>A | p.Asp204Asn | missense_variant | 6/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152144Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000499 AC: 125AN: 250594Hom.: 0 AF XY: 0.000694 AC XY: 94AN XY: 135502
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GnomAD4 exome AF: 0.000241 AC: 352AN: 1460942Hom.: 0 Cov.: 30 AF XY: 0.000323 AC XY: 235AN XY: 726756
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152262Hom.: 1 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome 11 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 14, 2021 | - - |
Uncertain significance, no assertion criteria provided | research | Division of Human Genetics, Children's Hospital of Philadelphia | May 24, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 08, 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
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;.;D
REVEL
Benign
Sift
Benign
T;.;T;.;.;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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