Genetic Variant AKAP9:p.Asn2223Lys (chr7-92076911-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005751.5(AKAP9):c.6669T>A(p.Asn2223Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. N2223N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Publications

1 publications found

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]

AKAP9 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
long QT syndrome 11
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
long QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

AKAP9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30952698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AKAP9	NM_005751.5	MANE Select	c.6669T>A	p.Asn2223Lys	missense	Exon 29 of 50	NP_005742.4
AKAP9	NM_147185.3		c.6645T>A	p.Asn2215Lys	missense	Exon 29 of 50	NP_671714.1
AKAP9	NM_001379277.1		c.1314T>A	p.Asn438Lys	missense	Exon 8 of 29	NP_001366206.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.6669T>A	p.Asn2223Lys	missense	Exon 29 of 50	ENSP00000348573.3
AKAP9	ENST00000491695.2	TSL:1	c.1314T>A	p.Asn438Lys	missense	Exon 8 of 29	ENSP00000494626.2
AKAP9	ENST00000394534.7	TSL:1	c.162T>A	p.Asn54Lys	missense	Exon 2 of 23	ENSP00000378042.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.036

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.2

PhyloP100

2.3

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.078

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.037

Vest4

0.36

MVP

0.54

MPC

0.27

ClinPred

0.98

GERP RS

4.4

Varity_R

0.23

gMVP

0.37

Mutation Taster

=66/34

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over