17-19909228-T-G

Variant names:

• chr17-19909228-T-G
• NM_007202.4:c.1936A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007202.4(AKAP10):​c.1936A>C​(p.Ile646Leu) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I646V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1765503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.1936A>C	p.Ile646Leu	missense_variant	Exon 14 of 15	ENST00000225737.11	NP_009133.2
AKAP10	NM_001330152.2	c.1762A>C	p.Ile588Leu	missense_variant	Exon 13 of 14		NP_001317081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.1936A>C	p.Ile646Leu	missense_variant	Exon 14 of 15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.1762A>C	p.Ile588Leu	missense_variant	Exon 13 of 14	5		ENSP00000378907.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		0.0010	B;B
Vest4		0.34
MutPred		0.32		Loss of catalytic residue at I646 (P = 0.0806);.;
MVP		0.18
MPC		0.21
ClinPred		0.77	D
GERP RS		5.9
Varity_R		0.28
gMVP		0.52

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: chr17-19812541;