rs1956993

Positions:

• chr14-32499820-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.325-35734G>A		intron_variant		ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.325-35734G>A		intron_variant		1	NM_004274.5	ENSP00000280979	P1

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

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.923

Alfa AF: 0.915 Hom.: 34471

Bravo AF: 0.927

Asia WGS AF: 0.949 AC: 3240 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.35

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: rs1956993; hg19: chr14-32969026;