Variant 6-151348900-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005100.4(AKAP12):c.509T>C(p.Ile170Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,613,968 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

AKAP12
NM_005100.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.61

Variant links:

Genes affected

AKAP12 (HGNC:370): (A-kinase anchoring protein 12) 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 is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

AKAP12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069877207).

BP6

Variant 6-151348900-T-C is Benign according to our data. Variant chr6-151348900-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 776173.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP12	NM_005100.4 linkuse as main transcript	c.509T>C	p.Ile170Thr	missense_variant	4/5	ENST00000402676.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP12	ENST00000402676.7 linkuse as main transcript	c.509T>C	p.Ile170Thr	missense_variant	4/5	5	NM_005100.4	A2	Q02952-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000422

AC:

106

AN:

251440

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00690

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.00168

AC:

255

AN:

152114

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00593

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000881

Hom.:

Bravo

AF:

0.00213

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000552

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;.;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N;.;.

MutationTaster

Benign

0.92

D;D;D;D

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.16

B;B;B;B

Vest4

0.39

MVP

0.31

MPC

0.23

ClinPred

0.11

GERP RS

5.5

Varity_R

0.26

gMVP

0.052

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over