NM_005751.5:c.5778C>T

Variant names:

• chr7-92062287-C-T
• rs10236397
• NM_005751.5:c.5778C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005751.5(AKAP9):​c.5778C>T​(p.Gly1926Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,607,738 control chromosomes in the GnomAD database, including 122,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G1926G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (12492 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110007 hom.)
• Consequence: AKAP9 NM_005751.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.273
• Publications: 24 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 7-92062287-C-T is Benign according to our data. Variant chr7-92062287-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 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.5778C>T	p.Gly1926Gly	synonymous	Exon 24 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.5778C>T	p.Gly1926Gly	synonymous	Exon 24 of 50	NP_671714.1	Q99996-3
	AKAP9	NM_001379277.1		c.423C>T	p.Gly141Gly	synonymous	Exon 3 of 29	NP_001366206.1	A0A2R8Y590

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.5778C>T	p.Gly1926Gly	synonymous	Exon 24 of 50	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000491695.2	TSL:1	c.423C>T	p.Gly141Gly	synonymous	Exon 3 of 29	ENSP00000494626.2	A0A2R8Y590
	AKAP9	ENST00000359028.7	TSL:5	c.5874C>T	p.Gly1958Gly	synonymous	Exon 25 of 51	ENSP00000351922.4	A0A0A0MRF6

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60817 AN: 151770 Hom.: 12480 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.410

GnomAD2 exomes AF: 0.375 AC: 94000 AN: 250612 AF XY: 0.378

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.309

Gnomad ASJ exome AF: 0.548

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.385 AC: 560291 AN: 1455850 Hom.: 110007 Cov.: 33 AF XY: 0.385 AC XY: 279161 AN XY: 724590

African (AFR) AF: 0.471 AC: 15693 AN: 33318

American (AMR) AF: 0.314 AC: 14034 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 14148 AN: 26086

East Asian (EAS) AF: 0.184 AC: 7311 AN: 39638

South Asian (SAS) AF: 0.389 AC: 33513 AN: 86094

European-Finnish (FIN) AF: 0.387 AC: 20649 AN: 53396

Middle Eastern (MID) AF: 0.426 AC: 2446 AN: 5746

European-Non Finnish (NFE) AF: 0.388 AC: 429058 AN: 1106706

Other (OTH) AF: 0.389 AC: 23439 AN: 60196

GnomAD4 genome AF: 0.401 AC: 60875 AN: 151888 Hom.: 12492 Cov.: 32 AF XY: 0.399 AC XY: 29605 AN XY: 74222

African (AFR) AF: 0.464 AC: 19221 AN: 41400

American (AMR) AF: 0.357 AC: 5450 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3472

East Asian (EAS) AF: 0.174 AC: 902 AN: 5172

South Asian (SAS) AF: 0.387 AC: 1868 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4076 AN: 10534

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26279 AN: 67920

Other (OTH) AF: 0.408 AC: 861 AN: 2108

Alfa AF: 0.400 Hom.: 22901

Bravo AF: 0.402

Asia WGS AF: 0.311 AC: 1084 AN: 3478

EpiCase AF: 0.392

EpiControl AF: 0.403

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Long QT syndrome 11 (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	4.4
DANN	Benign	0.66
PhyloP100		0.27
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10236397; hg19: chr7-91691601; COSMIC: COSV62341581;