chr7-92061756-G-T

Variant names:

• chr7-92061756-G-T
• rs2961024
• NM_005751.5:c.5764+334G>T

Variant summary

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

The NM_005751.5(AKAP9):​c.5764+334G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,320 control chromosomes in the GnomAD database, including 46,649 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 0.78 (46649 hom., cov: 28)
• Consequence: AKAP9 NM_005751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.5764+334G>T		intron_variant	Intron 23 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.5764+334G>T		intron_variant	Intron 23 of 49		NP_671714.1
AKAP9	NM_001379277.1	c.409+334G>T		intron_variant	Intron 2 of 28		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.5764+334G>T		intron_variant	Intron 23 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes AF: 0.778 AC: 117684 AN: 151200 Hom.: 46588 Cov.: 28

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.778 AC: 117801 AN: 151320 Hom.: 46649 Cov.: 28 AF XY: 0.780 AC XY: 57636 AN XY: 73920

African (AFR) AF: 0.930 AC: 38435 AN: 41320

American (AMR) AF: 0.787 AC: 11953 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2769 AN: 3468

East Asian (EAS) AF: 0.822 AC: 4228 AN: 5144

South Asian (SAS) AF: 0.792 AC: 3797 AN: 4794

European-Finnish (FIN) AF: 0.686 AC: 7109 AN: 10370

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47006 AN: 67738

Other (OTH) AF: 0.772 AC: 1622 AN: 2102

Alfa AF: 0.722 Hom.: 147794

Bravo AF: 0.790

Asia WGS AF: 0.848 AC: 2930 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.13
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: rs2961024; hg19: chr7-91691070;