rs759783541

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2

The NM_005751.5(AKAP9):​c.485G>A​(p.Ser162Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S162T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016426474).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKAP9NM_005751.5 linkuse as main transcriptc.485G>A p.Ser162Asn missense_variant 5/50 ENST00000356239.8
AKAP9NM_147185.3 linkuse as main transcriptc.485G>A p.Ser162Asn missense_variant 5/50

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKAP9ENST00000356239.8 linkuse as main transcriptc.485G>A p.Ser162Asn missense_variant 5/501 NM_005751.5 P4Q99996-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251338
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461828
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
8.3
DANN
Benign
0.64
DEOGEN2
Benign
0.23
.;.;T;T;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.73
T;T;T;T;T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.016
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
1.2
N;.;N;.;.;N
REVEL
Benign
0.059
Sift
Benign
1.0
T;.;T;.;.;T
Sift4G
Benign
1.0
.;T;T;T;.;T
Polyphen
0.0
.;.;B;.;.;.
Vest4
0.19
MutPred
0.20
Loss of phosphorylation at S162 (P = 0.0217);.;Loss of phosphorylation at S162 (P = 0.0217);Loss of phosphorylation at S162 (P = 0.0217);.;.;
MVP
0.10
MPC
0.051
ClinPred
0.022
T
GERP RS
-3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.017
gMVP
0.026

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759783541; hg19: chr7-91622278; API