NM_007202.4:c.1693A>G

Variant names:

• chr17-19924466-T-C
• rs781615376
• NM_007202.4:c.1693A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007202.4(AKAP10):​c.1693A>G​(p.Ile565Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12
• Publications: 0 publications found

Genes affected

AKAP10 (HGNC:368): (A-kinase anchoring protein 10) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32932276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007202.4. 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
	AKAP10	NM_007202.4	MANE Select	c.1693A>G	p.Ile565Val	missense	Exon 11 of 15	NP_009133.2
	AKAP10	NM_001330152.2		c.1519A>G	p.Ile507Val	missense	Exon 10 of 14	NP_001317081.1	E7EMD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP10	ENST00000225737.11	TSL:1 MANE Select	c.1693A>G	p.Ile565Val	missense	Exon 11 of 15	ENSP00000225737.6	O43572
	AKAP10	ENST00000395536.7	TSL:5	c.1519A>G	p.Ile507Val	missense	Exon 10 of 14	ENSP00000378907.3	E7EMD6
	AKAP10	ENST00000941090.1		c.1693A>G	p.Ile565Val	missense	Exon 11 of 16	ENSP00000611149.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.17
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.71	P
Vest4		0.44
MutPred		0.64		Gain of sheet (P = 0.0477)
MVP		0.36
MPC		0.32
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.33
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs781615376; hg19: chr17-19827779;