7-92040664-A-G

Variant names:

• chr7-92040664-A-G
• rs772968330
• NM_005751.5:c.4693-10A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005751.5(AKAP9):​c.4693-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 974,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AKAP9 NM_005751.5 intron
• Scores: Splicing: ADA: 0.0002398
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.4693-10A>G		intron_variant	Intron 17 of 49	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.4693-10A>G		intron_variant	Intron 17 of 49		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.4693-10A>G		intron_variant	Intron 17 of 49	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000205 AC: 2 AN: 974704 Hom.: 0 Cov.: 19 AF XY: 0.00000206 AC XY: 1 AN XY: 486508

African (AFR) AF: 0.00 AC: 0 AN: 20552

American (AMR) AF: 0.00 AC: 0 AN: 22586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30862

South Asian (SAS) AF: 0.00 AC: 0 AN: 47220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3214

European-Non Finnish (NFE) AF: 0.00000265 AC: 2 AN: 755120

Other (OTH) AF: 0.00 AC: 0 AN: 42390

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.58
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.0080
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: rs772968330; hg19: chr7-91669978;