chr6-151349203-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005100.4(AKAP12):c.812A>G(p.Glu271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,924 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0019 ( 6 hom., cov: 31)
Exomes 𝑓: 0.0031 ( 54 hom. )
Consequence
AKAP12
NM_005100.4 missense
NM_005100.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 2.28
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=0.00404191).
BP6
?
Variant 6-151349203-A-G is Benign according to our data. Variant chr6-151349203-A-G is described in ClinVar as [Benign]. Clinvar id is 721150.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00187 (285/152312) while in subpopulation SAS AF= 0.0214 (103/4820). AF 95% confidence interval is 0.018. There are 6 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP12 | NM_005100.4 | c.812A>G | p.Glu271Gly | missense_variant | 4/5 | ENST00000402676.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP12 | ENST00000402676.7 | c.812A>G | p.Glu271Gly | missense_variant | 4/5 | 5 | NM_005100.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00187 AC: 285AN: 152194Hom.: 6 Cov.: 31
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GnomAD3 exomes AF: 0.00432 AC: 1078AN: 249718Hom.: 20 AF XY: 0.00536 AC XY: 726AN XY: 135402
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GnomAD4 exome AF: 0.00307 AC: 4485AN: 1461612Hom.: 54 Cov.: 74 AF XY: 0.00382 AC XY: 2779AN XY: 727092
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GnomAD4 genome ? AF: 0.00187 AC: 285AN: 152312Hom.: 6 Cov.: 31 AF XY: 0.00212 AC XY: 158AN XY: 74488
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Asia WGS
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3478
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 | May 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;B
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