rs910318

chr14-32759092-A-Gchr14-32759092-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004274.5(AKAP6):c.3373-14586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,056 control chromosomes in the GnomAD database, including 32,041 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 0.63 (32041 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP6	NM_004274.5	c.3373-14586A>G		intron_variant		ENST00000280979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP6	ENST00000280979.9	c.3373-14586A>G		intron_variant		1	NM_004274.5	P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95156 AN: 151938 Hom.: 32017 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.626 AC: 95210 AN: 152056 Hom.: 32041 Cov.: 32 AF XY: 0.633 AC XY: 47067 AN XY: 74350

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.647

Alfa AF: 0.705 Hom.: 59215

Bravo AF: 0.612

Asia WGS AF: 0.733 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	17
Dann	Benign	0.85

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: rs910318; hg19: chr14-33228298;