7-91940976-G-C

Variant names:

• chr7-91940976-G-C
• rs4727267
• NM_005751.5:c.-124G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005751.5(AKAP9):​c.-124G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,022,494 control chromosomes in the GnomAD database, including 195,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26670 hom., cov: 34)
  • Exomes 𝑓: 0.62 (169104 hom.)
• Consequence: AKAP9 NM_005751.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.94
• Publications: 16 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

ENSG00000305226 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-91940976-G-C is Benign according to our data. Variant chr7-91940976-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 360809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 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.-124G>C		5_prime_UTR	Exon 1 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.-124G>C		5_prime_UTR	Exon 1 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.-124G>C		5_prime_UTR	Exon 1 of 50	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000394564.5	TSL:1	n.51G>C		non_coding_transcript_exon	Exon 1 of 7
	AKAP9	ENST00000681412.1		c.-124G>C		5_prime_UTR	Exon 1 of 49	ENSP00000506486.1	A0A7P0TBH8

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89266 AN: 152062 Hom.: 26662 Cov.: 34

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.620 AC: 539689 AN: 870314 Hom.: 169104 Cov.: 11 AF XY: 0.619 AC XY: 280801 AN XY: 453286

African (AFR) AF: 0.496 AC: 10863 AN: 21896

American (AMR) AF: 0.687 AC: 29198 AN: 42512

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 9914 AN: 21646

East Asian (EAS) AF: 0.816 AC: 29840 AN: 36562

South Asian (SAS) AF: 0.614 AC: 44933 AN: 73230

European-Finnish (FIN) AF: 0.614 AC: 31288 AN: 50922

Middle Eastern (MID) AF: 0.569 AC: 2607 AN: 4578

European-Non Finnish (NFE) AF: 0.616 AC: 356329 AN: 578266

Other (OTH) AF: 0.607 AC: 24717 AN: 40702

GnomAD4 genome AF: 0.587 AC: 89316 AN: 152180 Hom.: 26670 Cov.: 34 AF XY: 0.590 AC XY: 43885 AN XY: 74404

African (AFR) AF: 0.492 AC: 20417 AN: 41510

American (AMR) AF: 0.640 AC: 9787 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.826 AC: 4279 AN: 5178

South Asian (SAS) AF: 0.613 AC: 2960 AN: 4826

European-Finnish (FIN) AF: 0.614 AC: 6500 AN: 10580

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41691 AN: 67996

Other (OTH) AF: 0.579 AC: 1224 AN: 2114

Alfa AF: 0.505 Hom.: 1558

Bravo AF: 0.585

Asia WGS AF: 0.686 AC: 2383 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	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		1.9
PromoterAI		-0.029	Neutral
Mutation Taster		=171/129	polymorphism

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: rs4727267; hg19: chr7-91570290;