rs12533497

Variant names:

• chr7-92028358-G-A
• rs12533497
• NM_005751.5:c.4149-1537G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-92028358-G-A
• chr7-92028358-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005751.5(AKAP9):​c.4149-1537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 149,484 control chromosomes in the GnomAD database, including 46 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 0.0087 (46 hom., cov: 31)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.4149-1537G>A		intron_variant	Intron 14 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.4149-1537G>A		intron_variant	Intron 14 of 49		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.4149-1537G>A		intron_variant	Intron 14 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes AF: 0.00868 AC: 1297 AN: 149398 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.00185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.00275

Gnomad FIN AF: 0.00455

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000769

Gnomad OTH AF: 0.0112

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

GnomAD4 genome AF: 0.00868 AC: 1297 AN: 149484 Hom.: 46 Cov.: 31 AF XY: 0.00937 AC XY: 682 AN XY: 72812

Gnomad4 AFR AF: 0.00184

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.00276

Gnomad4 FIN AF: 0.00455

Gnomad4 NFE AF: 0.000769

Gnomad4 OTH AF: 0.0111

Alfa AF: 0.0149 Hom.: 45

Bravo AF: 0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.59

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: rs12533497; hg19: chr7-91657672;