chr7-92040664-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_005751.5(AKAP9):​c.4693-10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKAP9 NM_005751.5 intron
• Scores: Splicing: ADA: 0.0003154
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-92040664-A-C is Benign according to our data. Variant chr7-92040664-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3350014.Status of the report is no_assertion_criteria_provided, 0 stars.

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.4693-10A>C		intron	N/A	NP_005742.4
	AKAP9	NM_147185.3		c.4693-10A>C		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.4693-10A>C		intron	N/A	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000359028.7	TSL:5	c.4693-10A>C		intron	N/A	ENSP00000351922.4	A0A0A0MRF6
	AKAP9	ENST00000681412.1		c.4693-10A>C		intron	N/A	ENSP00000506486.1	A0A7P0TBH8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 974704 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 755120

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

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AKAP9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.0
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;