rs9206

Variant names:

• chr6-151358063-A-G
• rs9206
• NM_005100.4:c.*2349A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005100.4. 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
	AKAP12	NM_005100.4	MANE Select	c.*2349A>G		3_prime_UTR	Exon 5 of 5	NP_005091.2
	AKAP12	NM_144497.2		c.*2349A>G		3_prime_UTR	Exon 3 of 3	NP_653080.1
	AKAP12	NM_001370346.1		c.*2349A>G		3_prime_UTR	Exon 3 of 3	NP_001357275.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	ENST00000402676.7	TSL:5 MANE Select	c.*2349A>G		3_prime_UTR	Exon 5 of 5	ENSP00000384537.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.301 AC: 12483 AN: 41462

American (AMR) AF: 0.578 AC: 8825 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2132 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2347 AN: 5164

South Asian (SAS) AF: 0.431 AC: 2078 AN: 4818

European-Finnish (FIN) AF: 0.698 AC: 7371 AN: 10562

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.676 AC: 45956 AN: 67988

Other (OTH) AF: 0.559 AC: 1180 AN: 2110

Alfa AF: 0.627 Hom.: 16008

Bravo AF: 0.528

Asia WGS AF: 0.427 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.46
PhyloP100		-1.1
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: rs9206; hg19: chr6-151679198; COSMIC: COSV53572409; COSMIC: COSV53572409;