Variant X-50193913-G-A 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_003886.3(AKAP4):c.800C>T(p.Ala267Val) variant causes a missense change. The variant allele was found at a frequency of 0.000235 in 1,210,112 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00024 ( 0 hom. 92 hem. )

Consequence

AKAP4
NM_003886.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.69

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:

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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=0.041582942).

BP6

Variant X-50193913-G-A is Benign according to our data. Variant chrX-50193913-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2228945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP4	NM_003886.3 linkuse as main transcript	c.800C>T	p.Ala267Val	missense_variant	5/6	ENST00000358526.7	NP_003877.2
AKAP4	NM_139289.2 linkuse as main transcript	c.773C>T	p.Ala258Val	missense_variant	5/6		NP_647450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP4	ENST00000358526.7 linkuse as main transcript	c.800C>T	p.Ala267Val	missense_variant	5/6	1	NM_003886.3	ENSP00000351327		Q5JQC9-1

Frequencies

GnomAD3 genomes

AF:

0.000169

AC:

AN:

112101

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34247

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:

0.000562

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000319

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182867

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

67441

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000241

AC:

265

AN:

1098011

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

AN XY:

363383

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000169

AC:

AN:

112101

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34247

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000562

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000319

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.8

DANN

Benign

0.22

DEOGEN2

Benign

0.039

T;.

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.3

N;.

MutationTaster

Benign

0.99

D;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.082

Sift

Benign

0.68

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0010

B;.

Vest4

0.033

MVP

0.28

MPC

0.14

ClinPred

0.021

GERP RS

3.7

Varity_R

0.038

gMVP

0.12

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