17-19924468-G-T

Variant names:

• chr17-19924468-G-T
• rs142084873
• NM_007202.4:c.1691C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007202.4(AKAP10):​c.1691C>A​(p.Ala564Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4058869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.1691C>A	p.Ala564Glu	missense_variant	Exon 11 of 15	ENST00000225737.11	NP_009133.2
AKAP10	NM_001330152.2	c.1517C>A	p.Ala506Glu	missense_variant	Exon 10 of 14		NP_001317081.1
AKAP10	XR_007065258.1	n.1791-4350C>A		intron_variant	Intron 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.1691C>A	p.Ala564Glu	missense_variant	Exon 11 of 15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.1517C>A	p.Ala506Glu	missense_variant	Exon 10 of 14	5		ENSP00000378907.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247038 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133546

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000338

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453768 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.20
Sift	Benign	0.057	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.64		Loss of sheet (P = 0.0025);.;
MVP		0.26
MPC		0.26
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142084873; hg19: chr17-19827781;