chr6-151348777-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005100.4(AKAP12):​c.386C>A​(p.Ala129Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. A129V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Consequence

AKAP12
NM_005100.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0570
Variant links:
Genes affected
AKAP12 (HGNC:370): (A-kinase anchoring protein 12) 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. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042458206).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AKAP12NM_005100.4 linkc.386C>A p.Ala129Glu missense_variant Exon 4 of 5 ENST00000402676.7 NP_005091.2 Q02952-1Q86TJ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AKAP12ENST00000402676.7 linkc.386C>A p.Ala129Glu missense_variant Exon 4 of 5 5 NM_005100.4 ENSP00000384537.2 Q02952-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
54
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
1.1
DANN
Benign
0.85
DEOGEN2
Benign
0.035
T;T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.58
T;.;T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.042
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.26
N;N;.;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.50
N;N;N;N
REVEL
Benign
0.028
Sift
Benign
0.19
T;T;T;T
Sift4G
Benign
0.80
T;T;T;T
Polyphen
0.0030
B;B;B;B
Vest4
0.069
MutPred
0.12
Gain of solvent accessibility (P = 0.0488);Gain of solvent accessibility (P = 0.0488);.;.;
MVP
0.18
MPC
0.19
ClinPred
0.040
T
GERP RS
-3.0
Varity_R
0.060
gMVP
0.028

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1275973826; hg19: chr6-151669912; COSMIC: COSV99482350; API