NM_005100.4:c.1371T>C

Variant names:

• chr6-151349762-T-C
• rs900654
• NM_005100.4:c.1371T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005100.4(AKAP12):​c.1371T>C​(p.Ala457Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,613,870 control chromosomes in the GnomAD database, including 479,814 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 0.77 (45475 hom., cov: 30)
  • Exomes 𝑓: 0.77 (434339 hom.)
• Consequence: AKAP12 NM_005100.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 22 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 (AMR) allele frequency at 95% confidence interval = 0.787 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	NM_005100.4	MANE Select	c.1371T>C	p.Ala457Ala	synonymous	Exon 4 of 5	NP_005091.2
	AKAP12	NM_144497.2		c.1077T>C	p.Ala359Ala	synonymous	Exon 2 of 3	NP_653080.1	Q02952-2
	AKAP12	NM_001370346.1		c.1056T>C	p.Ala352Ala	synonymous	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.1371T>C	p.Ala457Ala	synonymous	Exon 4 of 5	ENSP00000384537.2	Q02952-1
	AKAP12	ENST00000253332.5	TSL:1	c.1371T>C	p.Ala457Ala	synonymous	Exon 3 of 4	ENSP00000253332.1	Q02952-1
	AKAP12	ENST00000354675.10	TSL:1	c.1077T>C	p.Ala359Ala	synonymous	Exon 2 of 3	ENSP00000346702.6	Q02952-2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117224 AN: 151884 Hom.: 45438 Cov.: 30

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.782

GnomAD2 exomes AF: 0.756 AC: 189948 AN: 251396 AF XY: 0.750

Gnomad AFR exome AF: 0.780

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.602

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.770 AC: 1125315 AN: 1461868 Hom.: 434339 Cov.: 75 AF XY: 0.767 AC XY: 557487 AN XY: 727238

African (AFR) AF: 0.779 AC: 26086 AN: 33480

American (AMR) AF: 0.799 AC: 35746 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 20810 AN: 26134

East Asian (EAS) AF: 0.668 AC: 26513 AN: 39700

South Asian (SAS) AF: 0.669 AC: 57704 AN: 86258

European-Finnish (FIN) AF: 0.781 AC: 41708 AN: 53406

Middle Eastern (MID) AF: 0.797 AC: 4596 AN: 5768

European-Non Finnish (NFE) AF: 0.779 AC: 866021 AN: 1112002

Other (OTH) AF: 0.764 AC: 46131 AN: 60396

GnomAD4 genome AF: 0.772 AC: 117316 AN: 152002 Hom.: 45475 Cov.: 30 AF XY: 0.771 AC XY: 57289 AN XY: 74294

African (AFR) AF: 0.781 AC: 32389 AN: 41474

American (AMR) AF: 0.798 AC: 12190 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3472

East Asian (EAS) AF: 0.610 AC: 3131 AN: 5134

South Asian (SAS) AF: 0.664 AC: 3189 AN: 4804

European-Finnish (FIN) AF: 0.787 AC: 8304 AN: 10552

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.779 AC: 52975 AN: 67984

Other (OTH) AF: 0.782 AC: 1649 AN: 2110

Alfa AF: 0.777 Hom.: 138218

Bravo AF: 0.774

Asia WGS AF: 0.654 AC: 2276 AN: 3478

EpiCase AF: 0.778

EpiControl AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.093
DANN	Benign	0.47
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs900654; hg19: chr6-151670897; COSMIC: COSV53576504; COSMIC: COSV53576504;