rs368967178

Variant names:

• chr7-92000970-A-G
• rs368967178
• NM_005751.5:c.1053A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005751.5(AKAP9):​c.1053A>G​(p.Lys351Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,533,734 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: AKAP9 NM_005751.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.03
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-92000970-A-G is Benign according to our data. Variant chr7-92000970-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 518710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

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.1053A>G	p.Lys351Lys	synonymous	Exon 8 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.1053A>G	p.Lys351Lys	synonymous	Exon 8 of 50	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.1053A>G	p.Lys351Lys	synonymous	Exon 8 of 50	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000359028.7	TSL:5	c.1053A>G	p.Lys351Lys	synonymous	Exon 8 of 51	ENSP00000351922.4	A0A0A0MRF6
	AKAP9	ENST00000681412.1		c.1053A>G	p.Lys351Lys	synonymous	Exon 8 of 49	ENSP00000506486.1	A0A7P0TBH8

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 366 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000582 AC: 84 AN: 144382 AF XY: 0.000475

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000247

GnomAD4 exome AF: 0.000230 AC: 318 AN: 1381446 Hom.: 2 Cov.: 30 AF XY: 0.000212 AC XY: 144 AN XY: 680812

African (AFR) AF: 0.00885 AC: 269 AN: 30386

American (AMR) AF: 0.000402 AC: 13 AN: 32320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24528

East Asian (EAS) AF: 0.00 AC: 0 AN: 35644

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1072352

Other (OTH) AF: 0.000576 AC: 33 AN: 57254

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74482

African (AFR) AF: 0.00851 AC: 354 AN: 41582

American (AMR) AF: 0.000588 AC: 9 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00123 Hom.: 0

Bravo AF: 0.00293

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.4
DANN	Benign	0.67
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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: rs368967178; hg19: chr7-91630284;