14-32577265-T-G

Position:

• chr14-32577265-T-G

Variant summary

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

The NM_004274.5(AKAP6):​c.2469+23T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,598,752 control chromosomes in the GnomAD database, including 350,669 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 0.65 (32561 hom., cov: 31)
  • Exomes 𝑓: 0.66 (318108 hom.)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.2469+23T>G		intron_variant		ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.2469+23T>G		intron_variant		1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557354.5	c.2469+23T>G		intron_variant		1		ENSP00000450531.1
AKAP6	ENST00000557272.1	c.2469+23T>G		intron_variant		5		ENSP00000451247.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99014 AN: 151724 Hom.: 32546 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.690

GnomAD3 exomes AF: 0.667 AC: 160133 AN: 239960 Hom.: 54178 AF XY: 0.669 AC XY: 86774 AN XY: 129650

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.745

Gnomad EAS exome AF: 0.866

Gnomad SAS exome AF: 0.681

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.655

Gnomad OTH exome AF: 0.662

GnomAD4 exome AF: 0.661 AC: 956799 AN: 1446912 Hom.: 318108 Cov.: 38 AF XY: 0.662 AC XY: 476368 AN XY: 719280

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.873

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.653

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.652 AC: 99075 AN: 151840 Hom.: 32561 Cov.: 31 AF XY: 0.655 AC XY: 48603 AN XY: 74186

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.691

Alfa AF: 0.662 Hom.: 70523

Bravo AF: 0.649

Asia WGS AF: 0.781 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs768787; hg19: chr14-33046471;