15-85645774-T-TG

Variant names:

• chr15-85645774-T-TG
• rs770591309
• NM_007200.5:c.4238-43dupG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_007200.5(AKAP13):​c.4238-43dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,427,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.35
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-85645774-T-TG is Benign according to our data. Variant chr15-85645774-T-TG is described in ClinVar as Likely_benign. ClinVar VariationId is 3056485.Status of the report is no_assertion_criteria_provided, 0 stars.

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.4238-43dupG		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.4238-43dupG		intron	N/A	NP_006729.4
	AKAP13	NM_001270546.1		c.158-43dupG		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.4238-44_4238-43insG		intron	N/A	ENSP00000378026.3	Q12802-1
	AKAP13	ENST00000361243.6	TSL:1	c.4238-44_4238-43insG		intron	N/A	ENSP00000354718.2	Q12802-2
	AKAP13	ENST00000560676.5	TSL:1	c.158-44_158-43insG		intron	N/A	ENSP00000481485.1	A0A087WY36

Frequencies

GnomAD3 genomes AF: 0.0000349 AC: 3 AN: 85890 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000340 AC: 4 AN: 117598 AF XY: 0.0000307

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000762

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000101

Gnomad NFE exome AF: 0.0000175

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000268 AC: 36 AN: 1341976 Hom.: 0 Cov.: 25 AF XY: 0.0000285 AC XY: 19 AN XY: 666904

African (AFR) AF: 0.00 AC: 0 AN: 27980

American (AMR) AF: 0.00 AC: 0 AN: 30102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22564

East Asian (EAS) AF: 0.00 AC: 0 AN: 37486

South Asian (SAS) AF: 0.0000403 AC: 3 AN: 74532

European-Finnish (FIN) AF: 0.0000233 AC: 1 AN: 42888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4838

European-Non Finnish (NFE) AF: 0.0000296 AC: 31 AN: 1046138

Other (OTH) AF: 0.0000180 AC: 1 AN: 55448

GnomAD4 genome AF: 0.0000349 AC: 3 AN: 85968 Hom.: 0 Cov.: 25 AF XY: 0.0000234 AC XY: 1 AN XY: 42812

African (AFR) AF: 0.0000536 AC: 1 AN: 18674

American (AMR) AF: 0.000109 AC: 1 AN: 9186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1842

East Asian (EAS) AF: 0.00 AC: 0 AN: 3324

South Asian (SAS) AF: 0.00 AC: 0 AN: 3174

European-Finnish (FIN) AF: 0.000139 AC: 1 AN: 7208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 144

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40738

Other (OTH) AF: 0.00 AC: 0 AN: 1184

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AKAP13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

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: rs770591309; hg19: chr15-86189005;