7-91940883-T-TGGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_005751.5(AKAP9):c.-202_-200dup variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0117 in 601,768 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (15 hom., cov: 34)
  • Exomes 𝑓: 0.012 (47 hom.)
• Consequence: AKAP9 NM_005751.5 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: 5.47

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]

LOC124901698 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 7-91940883-T-TGGC is Benign according to our data. Variant chr7-91940883-T-TGGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360806.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=2}.
• BS2: High AC in GnomAd at 1740 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP9	NM_005751.5	c.-202_-200dup		5_prime_UTR_variant	1/50	ENST00000356239.8
AKAP9	NM_147185.3	c.-202_-200dup		5_prime_UTR_variant	1/50
LOC124901698	XR_007060431.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP9	ENST00000356239.8	c.-202_-200dup		5_prime_UTR_variant	1/50	1	NM_005751.5	P4

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1740 AN: 152158 Hom.: 15 Cov.: 34

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.0118 AC: 5310 AN: 449492 Hom.: 47 Cov.: 4 AF XY: 0.0111 AC XY: 2662 AN XY: 239150

Gnomad4 AFR exome AF: 0.00229

Gnomad4 AMR exome AF: 0.00589

Gnomad4 ASJ exome AF: 0.000521

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00224

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0114 AC: 1742 AN: 152276 Hom.: 15 Cov.: 34 AF XY: 0.0130 AC XY: 968 AN XY: 74462

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.00331

Bravo AF: 0.00778

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	AKAP9: BS1, BS2 -

Congenital long QT syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371245265; hg19: chr7-91570197;