rs17522122

Positions:

• chr14-32833676-G-T

Variant summary

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

The NM_004274.5(AKAP6):​c.*3871G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,934 control chromosomes in the GnomAD database, including 13,664 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 0.42 (13664 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: AKAP6 NM_004274.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP6	NM_004274.5	c.*3871G>T		3_prime_UTR_variant	14/14	ENST00000280979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP6	ENST00000280979.9	c.*3871G>T		3_prime_UTR_variant	14/14	1	NM_004274.5	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63108 AN: 151816 Hom.: 13650 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.435

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.416 AC: 63140 AN: 151934 Hom.: 13664 Cov.: 32 AF XY: 0.413 AC XY: 30643 AN XY: 74232

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.442

Alfa AF: 0.450 Hom.: 4224

Bravo AF: 0.403

Asia WGS AF: 0.477 AC: 1656 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.34

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: rs17522122; hg19: chr14-33302882;