17-57105517-C-T

Variant names:

• chr17-57105517-C-T
• rs17761023
• NM_003488.4:c.53C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003488.4(AKAP1):​c.53C>T​(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,978 control chromosomes in the GnomAD database, including 8,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (766 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7909 hom.)
• Consequence: AKAP1 NM_003488.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019706786).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP1	NM_003488.4	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 11	ENST00000337714.8	NP_003479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP1	ENST00000337714.8	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 11	1	NM_003488.4	ENSP00000337736.3

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14175 AN: 152018 Hom.: 764 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.00964

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0867 AC: 21801 AN: 251310 AF XY: 0.0883

Gnomad AFR exome AF: 0.0698

Gnomad AMR exome AF: 0.0468

Gnomad ASJ exome AF: 0.0595

Gnomad EAS exome AF: 0.00625

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0921

GnomAD4 exome AF: 0.101 AC: 147812 AN: 1461844 Hom.: 7909 Cov.: 74 AF XY: 0.101 AC XY: 73189 AN XY: 727218

African (AFR) AF: 0.0678 AC: 2270 AN: 33480

American (AMR) AF: 0.0504 AC: 2254 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1588 AN: 26136

East Asian (EAS) AF: 0.0154 AC: 610 AN: 39700

South Asian (SAS) AF: 0.0707 AC: 6095 AN: 86256

European-Finnish (FIN) AF: 0.119 AC: 6359 AN: 53412

Middle Eastern (MID) AF: 0.0636 AC: 367 AN: 5768

European-Non Finnish (NFE) AF: 0.110 AC: 122797 AN: 1111976

Other (OTH) AF: 0.0906 AC: 5472 AN: 60394

GnomAD4 genome AF: 0.0932 AC: 14176 AN: 152134 Hom.: 766 Cov.: 32 AF XY: 0.0924 AC XY: 6869 AN XY: 74380

African (AFR) AF: 0.0708 AC: 2941 AN: 41530

American (AMR) AF: 0.0885 AC: 1352 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3468

East Asian (EAS) AF: 0.00966 AC: 50 AN: 5174

South Asian (SAS) AF: 0.0654 AC: 314 AN: 4804

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10584

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7598 AN: 67980

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.101 Hom.: 2456

Bravo AF: 0.0904

TwinsUK AF: 0.108 AC: 399

ALSPAC AF: 0.105 AC: 405

ESP6500AA AF: 0.0690 AC: 304

ESP6500EA AF: 0.102 AC: 879

ExAC AF: 0.0884 AC: 10734

Asia WGS AF: 0.0290 AC: 103 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;T;T;T;.;.;.;T;T;.;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T;.;.;T;T;T;T;.;.;T;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L;L;.;.;.;L;L;.;L;.
PhyloP100		3.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	.;N;.;.;.;.;.;.;N;.;D;.
REVEL	Benign	0.14
Sift	Pathogenic	0.0	.;D;.;.;.;.;.;.;D;.;D;.
Sift4G	Benign	0.11	T;D;D;D;T;T;T;D;D;T;T;T
Polyphen		0.55	.;P;P;P;.;.;.;P;P;.;.;.
Vest4		0.10, 0.10, 0.10, 0.10, 0.35
MPC		0.33
ClinPred		0.061	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.31
gMVP		0.83
Mutation Taster		=98/2	polymorphism (auto)

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: rs17761023; hg19: chr17-55182878; COSMIC: COSV58473318; COSMIC: COSV58473318;