rs9206

Positions:

• chr6-151358063-A-G

Variant summary

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

The NM_005100.4(AKAP12):​c.*2349A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,044 control chromosomes in the GnomAD database, including 24,758 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 0.55 (24758 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKAP12 NM_005100.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

AKAP12 (HGNC:370): (A-kinase anchoring protein 12) 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 expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP12	NM_005100.4	c.*2349A>G		3_prime_UTR_variant	5/5	ENST00000402676.7	NP_005091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP12	ENST00000402676.7	c.*2349A>G		3_prime_UTR_variant	5/5	5	NM_005100.4	ENSP00000384537	A2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82952 AN: 151926 Hom.: 24751 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.561

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.546 AC: 82978 AN: 152044 Hom.: 24758 Cov.: 32 AF XY: 0.544 AC XY: 40447 AN XY: 74318

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.559

Alfa AF: 0.628 Hom.: 14267

Bravo AF: 0.528

Asia WGS AF: 0.427 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.46

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: rs9206; hg19: chr6-151679198; COSMIC: COSV53572409; COSMIC: COSV53572409;