rs900654

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-151349762-T-A
• chr6-151349762-T-C
• chr6-151349762-T-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005100.4(AKAP12):​c.1371T>A​(p.Ala457Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-3.5 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP12	NM_005100.4	c.1371T>A	p.Ala457Ala	synonymous_variant	Exon 4 of 5	ENST00000402676.7	NP_005091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP12	ENST00000402676.7	c.1371T>A	p.Ala457Ala	synonymous_variant	Exon 4 of 5	5	NM_005100.4	ENSP00000384537.2
AKAP12	ENST00000253332.5	c.1371T>A	p.Ala457Ala	synonymous_variant	Exon 3 of 4	1		ENSP00000253332.1
AKAP12	ENST00000354675.10	c.1077T>A	p.Ala359Ala	synonymous_variant	Exon 2 of 3	1		ENSP00000346702.6
AKAP12	ENST00000359755.5	c.1056T>A	p.Ala352Ala	synonymous_variant	Exon 2 of 3	1		ENSP00000352794.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 138218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.077
DANN	Benign	0.65
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;