chr15-85533620-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_007200.5(AKAP13):c.218G>A(p.Cys73Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
AKAP13
NM_007200.5 missense
NM_007200.5 missense
Scores
8
5
4
Clinical Significance
Conservation
PhyloP100: 7.18
Genes affected
AKAP13 (HGNC:371): (A-kinase anchoring protein 13) 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. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.759
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP13 | NM_007200.5 | c.218G>A | p.Cys73Tyr | missense_variant | 4/37 | ENST00000394518.7 | |
AKAP13 | NM_006738.6 | c.218G>A | p.Cys73Tyr | missense_variant | 4/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP13 | ENST00000394518.7 | c.218G>A | p.Cys73Tyr | missense_variant | 4/37 | 1 | NM_007200.5 | A2 | |
AKAP13 | ENST00000361243.6 | c.218G>A | p.Cys73Tyr | missense_variant | 4/37 | 1 | A2 | ||
AKAP13 | ENST00000560302.5 | c.218G>A | p.Cys73Tyr | missense_variant | 4/4 | 1 | |||
AKAP13 | ENST00000559362.5 | c.218G>A | p.Cys73Tyr | missense_variant | 4/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
152220
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250834Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135608
GnomAD3 exomes
AF:
AC:
9
AN:
250834
Hom.:
AF XY:
AC XY:
5
AN XY:
135608
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461514Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727066
GnomAD4 exome
AF:
AC:
20
AN:
1461514
Hom.:
Cov.:
31
AF XY:
AC XY:
7
AN XY:
727066
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74374
GnomAD4 genome
?
AF:
AC:
6
AN:
152220
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74374
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
2
ExAC
?
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.218G>A (p.C73Y) alteration is located in exon 4 (coding exon 3) of the AKAP13 gene. This alteration results from a G to A substitution at nucleotide position 218, causing the cysteine (C) at amino acid position 73 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
Sift
Benign
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;D;D;D
Vest4
0.80, 0.90, 0.88
MVP
MPC
0.33
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at