15-85504055-C-T

Position:

• chr15-85504055-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394518.7(AKAP13):​c.34-17373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,892 control chromosomes in the GnomAD database, including 20,122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20122 hom., cov: 30)
• Consequence: AKAP13 ENST00000394518.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.34-17373C>T		intron_variant		ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.34-17373C>T		intron_variant			NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.34-17373C>T		intron_variant		1	NM_007200.5	ENSP00000378026	A2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77044 AN: 151770 Hom.: 20118 Cov.: 30

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.508 AC: 77091 AN: 151892 Hom.: 20122 Cov.: 30 AF XY: 0.501 AC XY: 37167 AN XY: 74232

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.541

Alfa AF: 0.533 Hom.: 3593

Bravo AF: 0.513

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.75

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: rs4281668; hg19: chr15-86047286;