14-32577265-T-G

Variant names:

• chr14-32577265-T-G
• rs768787
• NM_004274.5:c.2469+23T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004274.5. 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
	AKAP6	NM_004274.5	MANE Select	c.2469+23T>G		intron	N/A	NP_004265.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP6	ENST00000280979.9	TSL:1 MANE Select	c.2469+23T>G		intron	N/A	ENSP00000280979.4	Q13023-1
	AKAP6	ENST00000557354.5	TSL:1	c.2469+23T>G		intron	N/A	ENSP00000450531.1	Q13023-2
	AKAP6	ENST00000851220.1		c.2469+23T>G		intron	N/A	ENSP00000521279.1

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

GnomAD2 exomes AF: 0.667 AC: 160133 AN: 239960 AF XY: 0.669

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 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

African (AFR) AF: 0.597 AC: 19525 AN: 32720

American (AMR) AF: 0.595 AC: 24387 AN: 40980

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19242 AN: 25706

East Asian (EAS) AF: 0.873 AC: 34359 AN: 39336

South Asian (SAS) AF: 0.684 AC: 56385 AN: 82410

European-Finnish (FIN) AF: 0.668 AC: 35559 AN: 53242

Middle Eastern (MID) AF: 0.688 AC: 3939 AN: 5724

European-Non Finnish (NFE) AF: 0.653 AC: 722831 AN: 1106908

Other (OTH) AF: 0.677 AC: 40572 AN: 59886

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

African (AFR) AF: 0.603 AC: 24989 AN: 41414

American (AMR) AF: 0.629 AC: 9584 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2614 AN: 3468

East Asian (EAS) AF: 0.867 AC: 4468 AN: 5154

South Asian (SAS) AF: 0.692 AC: 3330 AN: 4812

European-Finnish (FIN) AF: 0.675 AC: 7115 AN: 10536

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44670 AN: 67914

Other (OTH) AF: 0.691 AC: 1458 AN: 2110

Alfa AF: 0.658 Hom.: 142409

Bravo AF: 0.649

Asia WGS AF: 0.781 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs768787; hg19: chr14-33046471;