17-19931878-G-A

Variant names:

• chr17-19931878-G-A
• rs11870360
• NM_007202.4:c.1568C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_007202.4(AKAP10):​c.1568C>T​(p.Ser523Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00328 in 1,614,032 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.018 (96 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (83 hom.)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.97

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031231642).
• BP6: Variant 17-19931878-G-A is Benign according to our data. Variant chr17-19931878-G-A is described in ClinVar as [Benign]. Clinvar id is 3041825.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.1568C>T	p.Ser523Leu	missense_variant	Exon 10 of 15	ENST00000225737.11	NP_009133.2
AKAP10	NM_001330152.2	c.1467+4408C>T		intron_variant	Intron 9 of 13		NP_001317081.1
AKAP10	XR_007065258.1	n.1717C>T		non_coding_transcript_exon_variant	Exon 10 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.1568C>T	p.Ser523Leu	missense_variant	Exon 10 of 15	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.1467+4408C>T		intron_variant	Intron 9 of 13	5		ENSP00000378907.3
AKAP10	ENST00000583951.1	c.-12C>T		upstream_gene_variant		3		ENSP00000463398.1
AKAP10	ENST00000578898.1	n.-2C>T		upstream_gene_variant		3		ENSP00000466329.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2741 AN: 152050 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00446 AC: 1121 AN: 251364 Hom.: 36 AF XY: 0.00330 AC XY: 448 AN XY: 135864

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00175 AC: 2558 AN: 1461864 Hom.: 83 Cov.: 31 AF XY: 0.00151 AC XY: 1101 AN XY: 727232

Gnomad4 AFR exome AF: 0.0645

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000764

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.0180 AC: 2744 AN: 152168 Hom.: 96 Cov.: 31 AF XY: 0.0170 AC XY: 1264 AN XY: 74380

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.00472

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00197 Hom.: 17

Bravo AF: 0.0202

ESP6500AA AF: 0.0672 AC: 296

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00577 AC: 700

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AKAP10-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.089
Sift	Benign	0.10	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.16
MPC		0.19
ClinPred		0.0087	T
GERP RS		4.9
Varity_R		0.057
gMVP		0.32

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: rs11870360; hg19: chr17-19835191;