rs10281556

Positions:

• chr7-92030739-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.4245+748A>G		intron_variant		ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.4245+748A>G		intron_variant			NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.4245+748A>G		intron_variant		1	NM_005751.5	ENSP00000348573	P4

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

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.410

Alfa AF: 0.393 Hom.: 3238

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

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: rs10281556; hg19: chr7-91660053;