rs10281556

Variant names:

• chr7-92030739-A-G
• rs10281556
• NM_005751.5:c.4245+748A>G

Variant summary

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

The NM_005751.5(AKAP9):​c.4245+748A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,776 control chromosomes in the GnomAD database, including 12,462 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 0.40 (12462 hom., cov: 31)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.4245+748A>G		intron_variant	Intron 15 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.4245+748A>G		intron_variant	Intron 15 of 49		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.4245+748A>G		intron_variant	Intron 15 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60732 AN: 151660 Hom.: 12450 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.401 AC: 60790 AN: 151776 Hom.: 12462 Cov.: 31 AF XY: 0.398 AC XY: 29549 AN XY: 74158

African (AFR) AF: 0.464 AC: 19180 AN: 41348

American (AMR) AF: 0.357 AC: 5449 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1885 AN: 3464

East Asian (EAS) AF: 0.174 AC: 898 AN: 5172

South Asian (SAS) AF: 0.387 AC: 1862 AN: 4810

European-Finnish (FIN) AF: 0.386 AC: 4044 AN: 10490

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26283 AN: 67932

Other (OTH) AF: 0.410 AC: 862 AN: 2102

Alfa AF: 0.393 Hom.: 5640

Bravo AF: 0.402

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.35
PhyloP100		0.35
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: rs10281556; hg19: chr7-91660053;