Variant 6-131160116-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016377.4(AKAP7):c.209G>A(p.Ser70Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AKAP7
NM_016377.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120

Variant links:

Genes affected

AKAP7 (HGNC:377): (A-kinase anchoring protein 7) This gene encodes a member of the A-kinase anchoring protein (AKAP) family, a group of functionally related proteins that bind to a regulatory subunit (RII) of cAMP-dependent protein kinase A (PKA) and target the enzyme to specific subcellular compartments. AKAPs have a common RII-binding domain, but contain different targeting motifs responsible for directing PKA to distinct intracellular locations. Three alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Apr 2011]

AKAP7 links:

AKAP7 (HGNC:):

AKAP7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081113786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP7	NM_016377.4 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	3/8	ENST00000431975.7	NP_057461.2	Q9P0M2-1Q2TAJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKAP7	ENST00000431975.7 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	3/8	2	NM_016377.4	ENSP00000405252.2	Q9P0M2-1
AKAP7	ENST00000683794.1 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	3/8			ENSP00000506952.1	A0A804HI88
AKAP7	ENST00000541650.5 linkuse as main transcript	c.206G>A	p.Ser69Asn	missense_variant	3/8	5		ENSP00000441048.1	F5GXD1
AKAP7	ENST00000366358.2 linkuse as main transcript	n.564G>A		non_coding_transcript_exon_variant	3/5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726064

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.:

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

May 02, 2024

The c.209G>A (p.S70N) alteration is located in exon 3 (coding exon 3) of the AKAP7 gene. This alteration results from a G to A substitution at nucleotide position 209, causing the serine (S) at amino acid position 70 to be replaced by an asparagine (N). 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

0.064

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.8

DANN

Benign

0.78

DEOGEN2

Benign

0.0047

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.041

Sift

Benign

0.59

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0010

B;.

Vest4

0.070

MutPred

0.32

Gain of relative solvent accessibility (P = 0.0166);.;

MVP

0.36

MPC

0.027

ClinPred

0.042

GERP RS

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.11

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