chr7-92044988-G-A

Variant names:

• chr7-92044988-G-A
• rs9785013
• NM_005751.5:c.5163-20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005751.5(AKAP9):​c.5163-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,570,554 control chromosomes in the GnomAD database, including 128,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16898 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111868 hom.)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.431
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-92044988-G-A is Benign according to our data. Variant chr7-92044988-G-A is described in ClinVar as Benign. ClinVar VariationId is 136331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	NM_005751.5	MANE Select	c.5163-20G>A		intron	N/A	NP_005742.4
	AKAP9	NM_147185.3		c.5163-20G>A		intron	N/A	NP_671714.1	Q99996-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.5163-20G>A		intron	N/A	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000359028.7	TSL:5	c.5259-20G>A		intron	N/A	ENSP00000351922.4	A0A0A0MRF6
	AKAP9	ENST00000681412.1		c.5163-20G>A		intron	N/A	ENSP00000506486.1	A0A7P0TBH8

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68922 AN: 151872 Hom.: 16861 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.452

GnomAD2 exomes AF: 0.391 AC: 97948 AN: 250218 AF XY: 0.391

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.548

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.392 AC: 556095 AN: 1418564 Hom.: 111868 Cov.: 27 AF XY: 0.392 AC XY: 277698 AN XY: 708534

African (AFR) AF: 0.655 AC: 21281 AN: 32504

American (AMR) AF: 0.323 AC: 14409 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 14044 AN: 25882

East Asian (EAS) AF: 0.205 AC: 8099 AN: 39474

South Asian (SAS) AF: 0.404 AC: 34487 AN: 85270

European-Finnish (FIN) AF: 0.387 AC: 20613 AN: 53318

Middle Eastern (MID) AF: 0.434 AC: 2459 AN: 5660

European-Non Finnish (NFE) AF: 0.389 AC: 416828 AN: 1072802

Other (OTH) AF: 0.404 AC: 23875 AN: 59030

GnomAD4 genome AF: 0.454 AC: 69017 AN: 151990 Hom.: 16898 Cov.: 32 AF XY: 0.451 AC XY: 33511 AN XY: 74270

African (AFR) AF: 0.644 AC: 26713 AN: 41474

American (AMR) AF: 0.377 AC: 5759 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1889 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5180

South Asian (SAS) AF: 0.402 AC: 1939 AN: 4820

European-Finnish (FIN) AF: 0.388 AC: 4080 AN: 10526

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26331 AN: 67954

Other (OTH) AF: 0.451 AC: 951 AN: 2108

Alfa AF: 0.411 Hom.: 20406

Bravo AF: 0.460

Asia WGS AF: 0.349 AC: 1216 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Long QT syndrome 11 (2)
-	-	1	Long QT syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		0.43
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: rs9785013; hg19: chr7-91674302; COSMIC: COSV62348317; COSMIC: COSV62348317;