7-92110149-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005751.5(AKAP9):​c.11714T>G​(p.Met3905Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000552 in 1,448,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88
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]
CYP51A1 (HGNC:2649): (cytochrome P450 family 51 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4189349).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AKAP9NM_005751.5 linkc.11714T>G p.Met3905Arg missense_variant Exon 50 of 50 ENST00000356239.8 NP_005742.4 Q99996-2Q6PJH3Q5GIA7
AKAP9NM_147185.3 linkc.11690T>G p.Met3897Arg missense_variant Exon 50 of 50 NP_671714.1 Q99996-3Q6PJH3Q5GIA7
AKAP9NM_001379277.1 linkc.6359T>G p.Met2120Arg missense_variant Exon 29 of 29 NP_001366206.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AKAP9ENST00000356239.8 linkc.11714T>G p.Met3905Arg missense_variant Exon 50 of 50 1 NM_005751.5 ENSP00000348573.3 Q99996-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000552
AC:
8
AN:
1448996
Hom.:
0
Cov.:
28
AF XY:
0.00000556
AC XY:
4
AN XY:
720022
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:
0.00000544
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Benign
0.93
DEOGEN2
Benign
0.34
.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.14
Sift
Uncertain
0.0010
D;.
Vest4
0.57
MVP
0.44
MPC
0.16
ClinPred
0.75
D
GERP RS
5.4
Varity_R
0.84
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-91739463; API