rs35359994

chr17-57106431-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003488.4(AKAP1):c.967G>A(p.Gly323Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,437,222 control chromosomes in the GnomAD database, including 2,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (374 hom., cov: 31)
  • Exomes 𝑓: 0.033 (2304 hom.)
• Consequence: AKAP1 NM_003488.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22

Genes affected

AKAP1 (HGNC:367): (A-kinase anchoring protein 1) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein binds to type I and type II regulatory subunits of PKA and anchors them to the mitochondrion. This protein is speculated to be involved in the cAMP-dependent signal transduction pathway and in directing RNA to a specific cellular compartment. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014906526).
• BP6: Variant 17-57106431-G-A is Benign according to our data. Variant chr17-57106431-G-A is described in ClinVar as [Benign]. Clinvar id is 770797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP1	NM_003488.4	c.967G>A	p.Gly323Ser	missense_variant	2/11	ENST00000337714.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP1	ENST00000337714.8	c.967G>A	p.Gly323Ser	missense_variant	2/11	1	NM_003488.4	P1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 8834 AN: 145222 Hom.: 374 Cov.: 31

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0437

Gnomad EAS AF: 0.00603

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0668

GnomAD3 exomes AF: 0.0202 AC: 4643 AN: 230220 Hom.: 269 AF XY: 0.0198 AC XY: 2458 AN XY: 124086

Gnomad AFR exome AF: 0.00656

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.00952

Gnomad EAS exome AF: 0.00306

Gnomad SAS exome AF: 0.0158

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0270

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0326 AC: 42173 AN: 1291882 Hom.: 2304 Cov.: 34 AF XY: 0.0340 AC XY: 21888 AN XY: 644010

Gnomad4 AFR exome AF: 0.00906

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0336

Gnomad4 EAS exome AF: 0.0136

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.0835

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0396

GnomAD4 genome AF: 0.0607 AC: 8829 AN: 145340 Hom.: 374 Cov.: 31 AF XY: 0.0597 AC XY: 4233 AN XY: 70924

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0437

Gnomad4 EAS AF: 0.00604

Gnomad4 SAS AF: 0.0430

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0661

Alfa AF: 0.0902 Hom.: 172

Bravo AF: 0.0758

TwinsUK AF: 0.104 AC: 385

ALSPAC AF: 0.104 AC: 399

ESP6500AA AF: 0.0188 AC: 83

ESP6500EA AF: 0.0706 AC: 607

ExAC AF: 0.0730 AC: 8826

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	5.3
Dann	Benign	0.72
DEOGEN2	Benign	0.094	T;T;T;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0076	N
MetaRNN	Benign	0.0015	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.030	N;.;.;.;N;N
REVEL	Benign	0.014
Sift	Benign	0.21	T;.;.;.;T;T
Sift4G	Benign	0.23	T;T;T;T;T;T
Polyphen		0.023	B;B;B;B;B;.
Vest4		0.029
MPC		0.23
ClinPred		0.0015	T
GERP RS		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.11

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: rs35359994; hg19: chr17-55183792; COSMIC: COSV58473107; COSMIC: COSV58473107;