Genetic Variant AKAP8:p.Gly263Arg (chr19-15372925-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP6

The NM_005858.4(AKAP8):c.787G>C(p.Gly263Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,372,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

AKAP8
NM_005858.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.53

Publications

3 publications found

Variant links:

Genes affected

AKAP8 (HGNC:378): (A-kinase anchoring protein 8) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins are scaffold proteins that contain a binding domain for the RI/RII subunit of protein kinase A (PKA) and recruit PKA and other signaling molecules to specific subcellular locations. This gene encodes a nuclear A-kinase anchor protein that binds to the RII alpha subunit of PKA and may play a role in chromosome condensation during mitosis by targeting PKA and the condensin complex to chromatin. A pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]

AKAP8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 19-15372925-C-G is Benign according to our data. Variant chr19-15372925-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 207849.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP8	NM_005858.4 link	c.787G>C	p.Gly263Arg	missense_variant	Exon 5 of 14	ENST00000269701.7	NP_005849.1	O43823

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP8	ENST00000269701.7 link	c.787G>C	p.Gly263Arg	missense_variant	Exon 5 of 14	1	NM_005858.4	ENSP00000269701.1		O43823

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1372602

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

673304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30534

American (AMR)

AF:

0.00

AC:

AN:

30620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20290

East Asian (EAS)

AF:

0.000129

AC:

AN:

38880

South Asian (SAS)

AF:

0.00

AC:

AN:

71838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5348

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069262

Other (OTH)

AF:

0.00

AC:

AN:

56416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Medical Research Institute, Tokyo Medical and Dental University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.82

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

PhyloP100

1.5

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.18

Sift

Benign

0.060

Sift4G

Uncertain

0.038

Polyphen

0.98

Vest4

0.56

MutPred

0.44

Gain of methylation at G263 (P = 0.0129);

MVP

0.40

MPC

0.63

ClinPred

0.97

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.53

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr19-15372925-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over