rs2108978

Variant names:

• chr17-19958145-C-A
• NM_007202.4:c.746G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-19958145-C-A
• chr17-19958145-C-G
• chr17-19958145-C-T

Variant summary

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

The NM_007202.4(AKAP10):​c.746G>T​(p.Arg249Leu) 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. 15/21 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. R249H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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=0.0784477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.746G>T	p.Arg249Leu	missense_variant	Exon 4 of 15	ENST00000225737.11	NP_009133.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.746G>T	p.Arg249Leu	missense_variant	Exon 4 of 15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.746G>T	p.Arg249Leu	missense_variant	Exon 4 of 14	5		ENSP00000378907.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.78
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.016
Sift	Benign	0.64	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	B;B
Vest4		0.23
MutPred		0.27		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.16
MPC		0.28
ClinPred		0.075	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.28

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: chr17-19861458;