rs147194783

chr7-92076938-A-Cchr7-92076938-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005751.5(AKAP9):c.6696A>C(p.Gln2232His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,146 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. Synonymous variant affecting the same amino acid position (i.e. Q2232Q) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: AKAP9 NM_005751.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3827575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP9	NM_005751.5	c.6696A>C	p.Gln2232His	missense_variant	29/50	ENST00000356239.8
AKAP9	NM_147185.3	c.6672A>C	p.Gln2224His	missense_variant	29/50
AKAP9	NM_001379277.1	c.1341A>C	p.Gln447His	missense_variant	8/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP9	ENST00000356239.8	c.6696A>C	p.Gln2232His	missense_variant	29/50	1	NM_005751.5	P4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.1	D;.;.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;.;.;D
Vest4		0.58
MVP		0.49
MPC		0.34
ClinPred		1.0	D
GERP RS		0.0018
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.65

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

Other links and lift over

dbSNP: rs147194783; hg19: chr7-91706252;