15-85653928-T-C

Position:

• chr15-85653928-T-C

Variant summary

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

The NM_007200.5(AKAP13):​c.4375-1489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,076 control chromosomes in the GnomAD database, including 43,605 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 0.75 (43605 hom., cov: 31)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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]

AKAP13-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.4375-1489T>C		intron_variant		ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.4375-1489T>C		intron_variant			NP_006729.4
AKAP13	NM_001270546.1	c.295-1489T>C		intron_variant			NP_001257475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.4375-1489T>C		intron_variant		1	NM_007200.5	ENSP00000378026.3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114269 AN: 151958 Hom.: 43550 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.752 AC: 114385 AN: 152076 Hom.: 43605 Cov.: 31 AF XY: 0.744 AC XY: 55295 AN XY: 74340

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.748

Alfa AF: 0.724 Hom.: 51763

Bravo AF: 0.764

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.63

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: rs338538; hg19: chr15-86197159;