rs2383376

chr14-32759675-C-T

Variant summary

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

The NM_004274.5(AKAP6):c.3373-14003C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,012 control chromosomes in the GnomAD database, including 8,860 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 0.28 (8860 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

Genes affected

AKAP6 (HGNC:376): (A-kinase anchoring protein 6) 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. The encoded protein is highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP6	NM_004274.5	c.3373-14003C>T		intron_variant		ENST00000280979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP6	ENST00000280979.9	c.3373-14003C>T		intron_variant		1	NM_004274.5	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43202 AN: 151894 Hom.: 8840 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.285 AC: 43256 AN: 152012 Hom.: 8860 Cov.: 32 AF XY: 0.276 AC XY: 20505 AN XY: 74318

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.245

Alfa AF: 0.189 Hom.: 3299

Bravo AF: 0.303

Asia WGS AF: 0.166 AC: 579 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	5.8
Dann	Benign	0.19

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: rs2383376; hg19: chr14-33228881;