chr6-151349152-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005100.4(AKAP12):c.761C>T(p.Pro254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,718 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.016 ( 79 hom., cov: 31)
Exomes 𝑓: 0.0017 ( 56 hom. )
Consequence
AKAP12
NM_005100.4 missense
NM_005100.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -0.177
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0019782484).
BP6
Variant 6-151349152-C-T is Benign according to our data. Variant chr6-151349152-C-T is described in ClinVar as [Benign]. Clinvar id is 768115.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP12 | NM_005100.4 | c.761C>T | p.Pro254Leu | missense_variant | 4/5 | ENST00000402676.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP12 | ENST00000402676.7 | c.761C>T | p.Pro254Leu | missense_variant | 4/5 | 5 | NM_005100.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0161 AC: 2441AN: 151942Hom.: 79 Cov.: 31
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GnomAD3 exomes AF: 0.00435 AC: 1087AN: 249772Hom.: 25 AF XY: 0.00332 AC XY: 449AN XY: 135380
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GnomAD4 exome AF: 0.00173 AC: 2533AN: 1461658Hom.: 56 Cov.: 74 AF XY: 0.00152 AC XY: 1104AN XY: 727118
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GnomAD4 genome AF: 0.0161 AC: 2445AN: 152060Hom.: 79 Cov.: 31 AF XY: 0.0161 AC XY: 1197AN XY: 74316
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 11, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;B
Vest4
MVP
MPC
ClinPred
T
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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