chr17-19958070-G-A

Variant names:

• chr17-19958070-G-A
• rs1171290302
• NM_007202.4:c.821C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007202.4(AKAP10):​c.821C>T​(p.Ala274Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08945006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.821C>T	p.Ala274Val	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.821C>T	p.Ala274Val	missense_variant	Exon 4 of 15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.821C>T	p.Ala274Val	missense_variant	Exon 4 of 14	5		ENSP00000378907.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.821C>T (p.A274V) alteration is located in exon 4 (coding exon 4) of the AKAP10 gene. This alteration results from a C to T substitution at nucleotide position 821, causing the alanine (A) at amino acid position 274 to be replaced by a valine (V). 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	Benign	0.089
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		4.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.032
Sift	Benign	0.31	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.21	B;B
Vest4		0.048
MutPred		0.33		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.22
MPC		0.22
ClinPred		0.42	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.36

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

Other links and lift over

dbSNP: rs1171290302; hg19: chr17-19861383;