NM_007200.5:c.4340C>G

Variant names:

• chr15-85645920-C-G
• rs748176498
• NM_007200.5:c.4340C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007200.5(AKAP13):​c.4340C>G​(p.Pro1447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,550 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (1 hom.)
• Consequence: AKAP13 NM_007200.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• 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]

AKAP13-AS1 (HGNC:55975): (AKAP13 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23902416).

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.4340C>G	p.Pro1447Arg	missense	Exon 10 of 37	NP_009131.2
	AKAP13	NM_006738.6		c.4340C>G	p.Pro1447Arg	missense	Exon 10 of 37	NP_006729.4
	AKAP13	NM_001270546.1		c.260C>G	p.Pro87Arg	missense	Exon 3 of 29	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.4340C>G	p.Pro1447Arg	missense	Exon 10 of 37	ENSP00000378026.3	Q12802-1
	AKAP13	ENST00000361243.6	TSL:1	c.4340C>G	p.Pro1447Arg	missense	Exon 10 of 37	ENSP00000354718.2	Q12802-2
	AKAP13	ENST00000560676.5	TSL:1	c.260C>G	p.Pro87Arg	missense	Exon 3 of 21	ENSP00000481485.1	A0A087WY36

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251190 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461550 Hom.: 1 Cov.: 35 AF XY: 0.0000179 AC XY: 13 AN XY: 727104

African (AFR) AF: 0.0000299 AC: 1 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.5
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.77	P
Vest4		0.44
MutPred		0.21		Loss of loop (P = 0.0603)
MVP		0.61
MPC		0.25
ClinPred		0.57	D
GERP RS		2.7
PromoterAI		0.054	Neutral
Varity_R		0.33
gMVP		0.36
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748176498; hg19: chr15-86189151;