rs3054057

Positions:

• chr15-85467306-ATGTT-A
• chr15-85467306-ATGTT-ATGTTTGTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_007200.5(AKAP13):​c.-11-18401_-11-18398del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (9153 hom., cov: 17)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

Genes affected

AKAP13 (HGNC:371): (A-kinase anchoring protein 13) 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. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP13	NM_007200.5	c.-11-18401_-11-18398del		intron_variant		ENST00000394518.7
AKAP13	NM_006738.6	c.-11-18401_-11-18398del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP13	ENST00000394518.7	c.-11-18401_-11-18398del		intron_variant		1	NM_007200.5	A2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45832 AN: 151706 Hom.: 9156 Cov.: 17

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45816 AN: 151824 Hom.: 9153 Cov.: 17 AF XY: 0.295 AC XY: 21919 AN XY: 74192

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.344

Alfa AF: 0.377 Hom.: 1523

Bravo AF: 0.288

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3054057; hg19: chr15-86010537;