Genetic Variant NM_001278309.2:c.2472G>A (chr12-4615829-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001278309.2(AKAP3):c.2472G>A(p.Val824Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 1,614,222 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 4 hom., cov: 33)

Exomes 𝑓: 0.010 ( 91 hom. )

Consequence

AKAP3
NM_001278309.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.647

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-4615829-C-T is Benign according to our data. Variant chr12-4615829-C-T is described in ClinVar as [Benign]. Clinvar id is 720004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.647 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP3	NM_001278309.2 link	c.2472G>A	p.Val824Val	synonymous_variant	Exon 6 of 6	ENST00000228850.6	NP_001265238.2	O75969V9HWD4
AKAP3	NM_006422.4 link	c.2472G>A	p.Val824Val	synonymous_variant	Exon 6 of 6		NP_006413.4	O75969V9HWD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKAP3	ENST00000228850.6 link	c.2472G>A	p.Val824Val	synonymous_variant	Exon 6 of 6	5	NM_001278309.2	ENSP00000228850.1	O75969
ENSG00000272921	ENST00000536588.1 link	n.141+10743C>T		intron_variant	Intron 1 of 6	3		ENSP00000445121.1	H0YGX0
AKAP3	ENST00000545990.6 link	c.2472G>A	p.Val824Val	synonymous_variant	Exon 6 of 6	2		ENSP00000440994.1	O75969

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

1075

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00626

AC:

1571

AN:

250946

Hom.:

AF XY:

0.00637

AC XY:

864

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00263

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00751

GnomAD4 exome

AF:

0.00995

AC:

14551

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00957

AC XY:

6962

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00568

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00320

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00783

GnomAD4 genome

AF:

0.00706

AC:

1075

AN:

152352

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

524

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00858

Hom.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AKAP3: BP4, BP7, BS1, BS2 -

Mar 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.72

DANN

Benign

0.69

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