Genetic Variant AKAP1:p.Ala90Val (chr17-57105733-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003488.4(AKAP1):c.269C>T(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

AKAP1
NM_003488.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21

Publications

0 publications found

Variant links:

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]

AKAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02703926).

BP6

Variant 17-57105733-C-T is Benign according to our data. Variant chr17-57105733-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2476164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003488.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKAP1	NM_003488.4	MANE Select	c.269C>T	p.Ala90Val	missense	Exon 2 of 11	NP_003479.1	A0A140VK05
AKAP1	NM_001242902.2		c.269C>T	p.Ala90Val	missense	Exon 3 of 12	NP_001229831.1	Q92667-1
AKAP1	NM_001242903.2		c.269C>T	p.Ala90Val	missense	Exon 3 of 12	NP_001229832.1	Q92667-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKAP1	ENST00000337714.8	TSL:1 MANE Select	c.269C>T	p.Ala90Val	missense	Exon 2 of 11	ENSP00000337736.3	Q92667-1
AKAP1	ENST00000314126.4	TSL:1	c.269C>T	p.Ala90Val	missense	Exon 2 of 7	ENSP00000314075.3	Q92667-2
AKAP1	ENST00000964437.1		c.269C>T	p.Ala90Val	missense	Exon 2 of 12	ENSP00000634496.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251420

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1112012

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0090

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.057

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.62

M_CAP

Benign

0.0090

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

PhyloP100

-1.2

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.11

REVEL

Benign

0.017

Sift

Benign

0.64

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.0090

MutPred

0.084

Loss of relative solvent accessibility (P = 0.0186)

MVP

0.26

MPC

0.24

ClinPred

0.050

GERP RS

-7.9

PromoterAI

0.0056

Neutral

(source)

Varity_R

0.016

gMVP

0.093

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over