6-151348777-C-A

Variant names:

• chr6-151348777-C-A
• rs1275973826
• NM_005100.4:c.386C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005100.4(AKAP12):​c.386C>A​(p.Ala129Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A129V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AKAP12 NM_005100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042458206).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	NM_005100.4	MANE Select	c.386C>A	p.Ala129Glu	missense	Exon 4 of 5	NP_005091.2
	AKAP12	NM_144497.2		c.92C>A	p.Ala31Glu	missense	Exon 2 of 3	NP_653080.1	Q02952-2
	AKAP12	NM_001370346.1		c.71C>A	p.Ala24Glu	missense	Exon 2 of 3	NP_001357275.1	Q02952-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	ENST00000402676.7	TSL:5 MANE Select	c.386C>A	p.Ala129Glu	missense	Exon 4 of 5	ENSP00000384537.2	Q02952-1
	AKAP12	ENST00000253332.5	TSL:1	c.386C>A	p.Ala129Glu	missense	Exon 3 of 4	ENSP00000253332.1	Q02952-1
	AKAP12	ENST00000354675.10	TSL:1	c.92C>A	p.Ala31Glu	missense	Exon 2 of 3	ENSP00000346702.6	Q02952-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.85
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.057
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.028
Sift	Benign	0.19	T
Sift4G	Benign	0.80	T
Polyphen		0.0030	B
Vest4		0.069
MutPred		0.12		Gain of solvent accessibility (P = 0.0488)
MVP		0.18
MPC		0.19
ClinPred		0.040	T
GERP RS		-3.0
Varity_R		0.060
gMVP		0.028
Mutation Taster		=96/4	polymorphism

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: rs1275973826; hg19: chr6-151669912; COSMIC: COSV99482350;