rs10499266

chr6-151251388-G-Achr6-151251388-G-C

Variant summary

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

The NM_005100.4(AKAP12):c.162+10664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 152,238 control chromosomes in the GnomAD database, including 777 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 0.084 (777 hom., cov: 32)
• Consequence: AKAP12 NM_005100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP12	NM_005100.4	c.162+10664G>A		intron_variant		ENST00000402676.7
AKAP12	XM_017011517.3	c.162+10664G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP12	ENST00000402676.7	c.162+10664G>A		intron_variant		5	NM_005100.4	A2
AKAP12	ENST00000253332.5	c.162+10664G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12753 AN: 152118 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0692

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

GnomAD4 genome AF: 0.0838 AC: 12757 AN: 152238 Hom.: 777 Cov.: 32 AF XY: 0.0890 AC XY: 6628 AN XY: 74432

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0673 Hom.: 560

Bravo AF: 0.0722

Asia WGS AF: 0.221 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.0
Dann	Benign	0.74

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: rs10499266; hg19: chr6-151572523;