15-85455510-T-C

Variant names:

• chr15-85455510-T-C
• rs12443473
• NM_007200.5:c.-11-30200T>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.-11-30200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,964 control chromosomes in the GnomAD database, including 9,413 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 0.29 (9413 hom., cov: 31)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.-11-30200T>C		intron_variant	Intron 1 of 36	ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.-11-30200T>C		intron_variant	Intron 1 of 36		NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.-11-30200T>C		intron_variant	Intron 1 of 36	1	NM_007200.5	ENSP00000378026.3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44476 AN: 151848 Hom.: 9399 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.293 AC: 44549 AN: 151964 Hom.: 9413 Cov.: 31 AF XY: 0.291 AC XY: 21614 AN XY: 74294

African (AFR) AF: 0.586 AC: 24234 AN: 41388

American (AMR) AF: 0.364 AC: 5548 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.194 AC: 999 AN: 5160

South Asian (SAS) AF: 0.144 AC: 694 AN: 4808

European-Finnish (FIN) AF: 0.150 AC: 1588 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10263 AN: 67998

Other (OTH) AF: 0.265 AC: 559 AN: 2106

Alfa AF: 0.174 Hom.: 2256

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.30
PhyloP100		-0.34
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: rs12443473; hg19: chr15-85998741;