rs2108978

chr17-19958145-C-Gchr17-19958145-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>C(p.Arg249Pro) 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=0.07916659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP10	NM_007202.4	c.746G>C	p.Arg249Pro	missense_variant	4/15	ENST00000225737.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP10	ENST00000225737.11	c.746G>C	p.Arg249Pro	missense_variant	4/15	1	NM_007202.4	P1
AKAP10	ENST00000395536.7	c.746G>C	p.Arg249Pro	missense_variant	4/14	5
AKAP10	ENST00000582611.5	c.*289G>C		3_prime_UTR_variant, NMD_transcript_variant	4/7	5
AKAP10	ENST00000474245.1			upstream_gene_variant		2

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	0.075
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.94
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.014
Sift	Benign	0.23	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0010	B;B
Vest4		0.10
MutPred		0.35		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.12
MPC		0.31
ClinPred		0.059	T
GERP RS		2.4
Varity_R		0.14
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs2108978; hg19: chr17-19861458;