Variant 6-131145290-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016377.4(AKAP7):c.25A>G(p.Ile9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AKAP7
NM_016377.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.398

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052790582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4 linkuse as main transcript	c.25A>G	p.Ile9Val	missense_variant	2/8	ENST00000431975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP7	ENST00000431975.7 linkuse as main transcript	c.25A>G	p.Ile9Val	missense_variant	2/8	2	NM_016377.4	P1	Q9P0M2-1
AKAP7	ENST00000683794.1 linkuse as main transcript	c.25A>G	p.Ile9Val	missense_variant	2/8
AKAP7	ENST00000541650.5 linkuse as main transcript	c.22A>G	p.Ile8Val	missense_variant, splice_region_variant	2/8	5
AKAP7	ENST00000366358.2 linkuse as main transcript	n.380A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1349472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670966

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Jun 26, 2023

The c.25A>G (p.I9V) alteration is located in exon 2 (coding exon 2) of the AKAP7 gene. This alteration results from a A to G substitution at nucleotide position 25, causing the isoleucine (I) at amino acid position 9 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.67

DANN

Benign

0.63

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.052

Sift

Benign

0.45

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0010

B;.

Vest4

0.068

MutPred

0.16

Loss of helix (P = 0.1299);.;

MVP

0.27

MPC

0.026

ClinPred

0.054

GERP RS

-8.5

Varity_R

0.025

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over