Genetic Variant NM_003886.3:c.1489G>A (chrX-50193224-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_003886.3(AKAP4):c.1489G>A(p.Gly497Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,209,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 18 hem. )

Consequence

AKAP4
NM_003886.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.42

Publications

0 publications found

Variant links:

Genes affected

AKAP4 (HGNC:374): (A-kinase anchoring protein 4) 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 localized to the sperm flagellum and may be involved in the regulation of sperm motility. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

AKAP4 links:

ENSG00000301433 (HGNC:):

ENSG00000301433 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07558912).

BP6

Variant X-50193224-C-T is Benign according to our data. Variant chrX-50193224-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3515031.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003886.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP4	NM_003886.3	MANE Select	c.1489G>A	p.Gly497Ser	missense	Exon 5 of 6	NP_003877.2
	AKAP4	NM_139289.2		c.1462G>A	p.Gly488Ser	missense	Exon 5 of 6	NP_647450.1	Q5JQC9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKAP4	ENST00000358526.7	TSL:1 MANE Select	c.1489G>A	p.Gly497Ser	missense	Exon 5 of 6	ENSP00000351327.2	Q5JQC9-1
AKAP4	ENST00000376064.7	TSL:1	c.1462G>A	p.Gly488Ser	missense	Exon 5 of 6	ENSP00000365232.3	Q5JQC9-2
AKAP4	ENST00000481402.5	TSL:1	n.1601G>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111863

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000328

AC:

AN:

182667

AF XY:

0.0000149

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:

0.0000737

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1097970

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

363342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54125

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000653

AC:

AN:

842031

Other (OTH)

AF:

0.00

AC:

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000447

AC:

AN:

111863

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34033

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30765

American (AMR)

AF:

0.00

AC:

AN:

10564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.000281

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2637

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6107

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53174

Other (OTH)

AF:

0.00

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

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

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0040

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.71

M_CAP

Benign

0.0076

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

PhyloP100

-2.4

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.65

REVEL

Benign

0.065

Sift

Benign

0.35

Sift4G

Benign

0.22

Polyphen

0.56

Vest4

0.077

MutPred

0.64

Gain of phosphorylation at G497 (P = 0.0677)

MVP

0.40

MPC

0.17

ClinPred

0.041

GERP RS

-4.5

Varity_R

0.069

gMVP

0.14

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over