chr7-91990782-G-A

Variant names:

• chr7-91990782-G-A
• rs7808587
• NM_005751.5:c.352-1376G>A

Variant summary

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

The NM_005751.5(AKAP9):​c.352-1376G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,058 control chromosomes in the GnomAD database, including 26,037 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 0.57 (26037 hom., cov: 33)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.352-1376G>A		intron_variant	Intron 3 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.352-1376G>A		intron_variant	Intron 3 of 49		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.352-1376G>A		intron_variant	Intron 3 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86642 AN: 151940 Hom.: 25985 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.570 AC: 86747 AN: 152058 Hom.: 26037 Cov.: 33 AF XY: 0.569 AC XY: 42299 AN XY: 74300

African (AFR) AF: 0.774 AC: 32120 AN: 41502

American (AMR) AF: 0.482 AC: 7363 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2928 AN: 5176

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4826

European-Finnish (FIN) AF: 0.476 AC: 5020 AN: 10540

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32825 AN: 67946

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

Alfa AF: 0.537 Hom.: 7892

Bravo AF: 0.581

Asia WGS AF: 0.547 AC: 1902 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.49
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: rs7808587; hg19: chr7-91620096;