rs11772585

Variant names:

• chr7-91952189-C-T
• rs11772585
• NM_005751.5:c.48+11042C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005751.5(AKAP9):​c.48+11042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,204 control chromosomes in the GnomAD database, including 1,109 homozygotes. 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: 𝑓 0.11 (1109 hom., cov: 33)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.48+11042C>T		intron_variant	Intron 1 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.48+11042C>T		intron_variant	Intron 1 of 49		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.48+11042C>T		intron_variant	Intron 1 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17310 AN: 152086 Hom.: 1106 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17313 AN: 152204 Hom.: 1109 Cov.: 33 AF XY: 0.115 AC XY: 8563 AN XY: 74420

African (AFR) AF: 0.126 AC: 5227 AN: 41532

American (AMR) AF: 0.105 AC: 1604 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1808 AN: 5174

South Asian (SAS) AF: 0.0997 AC: 481 AN: 4826

European-Finnish (FIN) AF: 0.0894 AC: 946 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0956 AC: 6503 AN: 68014

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.108 Hom.: 1673

Bravo AF: 0.119

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11772585; hg19: chr7-91581503;