Variant 6-131145304-G-C 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_001387863.1(AKAP7):c.-28G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,531,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

AKAP7
NM_001387863.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0840

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:

Genome browser will be placed here

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=0.048589855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP7	NM_016377.4 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	2/8	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.39G>C	p.Glu13Asp	missense_variant	2/8	2	NM_016377.4	ENSP00000405252.2	Q9P0M2-1
AKAP7	ENST00000683794.1 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	2/8			ENSP00000506952.1	A0A804HI88
AKAP7	ENST00000541650.5 linkuse as main transcript	c.36G>C	p.Glu12Asp	missense_variant	2/8	5		ENSP00000441048.1	F5GXD1
AKAP7	ENST00000366358.2 linkuse as main transcript	n.394G>C		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

224050

Hom.:

AF XY:

0.0000164

AC XY:

AN XY:

122014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000281

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000652

AC:

AN:

1379494

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

686612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

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:

0.00000752

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Dec 06, 2022

The c.39G>C (p.E13D) alteration is located in exon 2 (coding exon 2) of the AKAP7 gene. This alteration results from a G to C substitution at nucleotide position 39, causing the glutamic acid (E) at amino acid position 13 to be replaced by an aspartic acid (D). 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

0.088

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.5

DANN

Benign

0.95

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.072

Sift

Benign

0.13

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.099

B;.

Vest4

0.26

MutPred

0.085

Gain of loop (P = 0.069);.;

MVP

0.37

MPC

0.029

ClinPred

0.033

GERP RS

-0.85

Varity_R

0.048

gMVP

0.080

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