chr14-32412040-T-G

Variant names:

• chr14-32412040-T-G
• rs8013938
• NM_004274.5:c.-34-21420T>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.-34-21420T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,850 control chromosomes in the GnomAD database, including 32,925 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 (32925 hom., cov: 31)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 3 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]

ENSG00000258580 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.-34-21420T>G		intron_variant	Intron 1 of 13	ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.-34-21420T>G		intron_variant	Intron 1 of 13	1	NM_004274.5	ENSP00000280979.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96242 AN: 151732 Hom.: 32918 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.634 AC: 96286 AN: 151850 Hom.: 32925 Cov.: 31 AF XY: 0.633 AC XY: 46939 AN XY: 74184

African (AFR) AF: 0.401 AC: 16607 AN: 41400

American (AMR) AF: 0.727 AC: 11098 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2727 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5160

South Asian (SAS) AF: 0.548 AC: 2640 AN: 4814

European-Finnish (FIN) AF: 0.768 AC: 8078 AN: 10514

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.763 AC: 51856 AN: 67928

Other (OTH) AF: 0.673 AC: 1418 AN: 2108

Alfa AF: 0.671 Hom.: 5197

Bravo AF: 0.624

Asia WGS AF: 0.351 AC: 1220 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.83
PhyloP100		0.046
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: rs8013938; hg19: chr14-32881246;