chr17-19939816-G-T

Position:

• chr17-19939816-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_007202.4(AKAP10):​c.1219C>A​(p.Gln407Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000055 (0 hom.)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.59

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]

AKAP10 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.1219C>A	p.Gln407Lys	missense_variant	8/15	ENST00000225737.11	NP_009133.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.1219C>A	p.Gln407Lys	missense_variant	8/15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.1219C>A	p.Gln407Lys	missense_variant	8/14	5		ENSP00000378907.3
AKAP10	ENST00000460046.2	n.*9C>A		non_coding_transcript_exon_variant	3/4	3		ENSP00000464294.1
AKAP10	ENST00000460046.2	n.*9C>A		3_prime_UTR_variant	3/4	3		ENSP00000464294.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461610 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.1219C>A (p.Q407K) alteration is located in exon 8 (coding exon 8) of the AKAP10 gene. This alteration results from a C to A substitution at nucleotide position 1219, causing the glutamine (Q) at amino acid position 407 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.54
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.064	T;D
Polyphen		1.0	D;D
Vest4		0.94
MutPred		0.76		Gain of methylation at Q407 (P = 0.014);Gain of methylation at Q407 (P = 0.014);
MVP		0.80
MPC		0.91
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.42
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-19843129;