15-85653928-T-C

Variant names:

• chr15-85653928-T-C
• rs338538
• NM_007200.5:c.4375-1489T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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:55975): (AKAP13 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007200.5. 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
	AKAP13	NM_007200.5	MANE Select	c.4375-1489T>C		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.4375-1489T>C		intron	N/A	NP_006729.4
	AKAP13	NM_001270546.1		c.295-1489T>C		intron	N/A	NP_001257475.1	B0AZU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP13	ENST00000394518.7	TSL:1 MANE Select	c.4375-1489T>C		intron	N/A	ENSP00000378026.3	Q12802-1
	AKAP13	ENST00000361243.6	TSL:1	c.4375-1489T>C		intron	N/A	ENSP00000354718.2	Q12802-2
	AKAP13	ENST00000560676.5	TSL:1	c.295-1489T>C		intron	N/A	ENSP00000481485.1	A0A087WY36

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

African (AFR) AF: 0.890 AC: 36932 AN: 41484

American (AMR) AF: 0.702 AC: 10723 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2822 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3246 AN: 5154

South Asian (SAS) AF: 0.579 AC: 2793 AN: 4822

European-Finnish (FIN) AF: 0.624 AC: 6585 AN: 10556

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48748 AN: 67998

Other (OTH) AF: 0.748 AC: 1580 AN: 2112

Alfa AF: 0.730 Hom.: 67001

Bravo AF: 0.764

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs338538; hg19: chr15-86197159;