NM_004274.5:c.325-35734G>A

Variant names:

• chr14-32499820-G-A
• rs1956993
• NM_004274.5:c.325-35734G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004274.5(AKAP6):​c.325-35734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 151,948 control chromosomes in the GnomAD database, including 65,205 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 0.93 (65205 hom., cov: 31)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP6	NM_004274.5	MANE Select	c.325-35734G>A		intron	N/A	NP_004265.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP6	ENST00000280979.9	TSL:1 MANE Select	c.325-35734G>A		intron	N/A	ENSP00000280979.4
	AKAP6	ENST00000557354.5	TSL:1	c.325-35734G>A		intron	N/A	ENSP00000450531.1
	AKAP6	ENST00000557272.1	TSL:5	c.325-35734G>A		intron	N/A	ENSP00000451247.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140552 AN: 151828 Hom.: 65151 Cov.: 31

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.926 AC: 140665 AN: 151948 Hom.: 65205 Cov.: 31 AF XY: 0.926 AC XY: 68740 AN XY: 74260

African (AFR) AF: 0.975 AC: 40454 AN: 41486

American (AMR) AF: 0.899 AC: 13685 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.948 AC: 4909 AN: 5178

South Asian (SAS) AF: 0.933 AC: 4496 AN: 4818

European-Finnish (FIN) AF: 0.903 AC: 9505 AN: 10522

Middle Eastern (MID) AF: 0.885 AC: 255 AN: 288

European-Non Finnish (NFE) AF: 0.903 AC: 61377 AN: 67942

Other (OTH) AF: 0.923 AC: 1952 AN: 2114

Alfa AF: 0.914 Hom.: 46413

Bravo AF: 0.927

Asia WGS AF: 0.949 AC: 3240 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.35
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs1956993; hg19: chr14-32969026;