Variant 12-4627140-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001278309.2(AKAP3):c.1762A>G(p.Lys588Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AKAP3
NM_001278309.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

Variant links:

Genes affected

AKAP3 (HGNC:373): (A-kinase anchoring protein 3) This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is reported to participate in protein-protein interactions with the R-subunit of the protein kinase A as well as sperm-associated proteins. This protein is expressed in spermatozoa and localized to the acrosomal region of the sperm head as well as the length of the principal piece. It may function as a regulator of motility, capacitation, and the acrosome reaction. [provided by RefSeq, May 2013]

AKAP3 links:

ENSG00000272921 (HGNC:):

ENSG00000272921 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP3	NM_001278309.2 link	c.1762A>G	p.Lys588Glu	missense_variant	5/6	ENST00000228850.6	NP_001265238.2	O75969V9HWD4
AKAP3	NM_006422.4 link	c.1762A>G	p.Lys588Glu	missense_variant	5/6		NP_006413.4	O75969V9HWD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKAP3	ENST00000228850.6 link	c.1762A>G	p.Lys588Glu	missense_variant	5/6	5	NM_001278309.2	ENSP00000228850.1	O75969
ENSG00000272921	ENST00000536588.1 link	n.142-4182T>C		intron_variant		3		ENSP00000445121.1	H0YGX0
AKAP3	ENST00000545990.6 link	c.1762A>G	p.Lys588Glu	missense_variant	5/6	2		ENSP00000440994.1	O75969

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251152

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.1762A>G (p.K588E) alteration is located in exon 4 (coding exon 2) of the AKAP3 gene. This alteration results from a A to G substitution at nucleotide position 1762, causing the lysine (K) at amino acid position 588 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.17

Sift

Benign

0.24

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.99

D;D

Vest4

0.42

MutPred

0.53

Loss of ubiquitination at K588 (P = 0.0098);Loss of ubiquitination at K588 (P = 0.0098);

MVP

0.51

MPC

0.67

ClinPred

0.86

GERP RS

4.8

Varity_R

0.15

gMVP

0.19

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