Variant 6-131219726-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016377.4(AKAP7):c.768A>G(p.Ile256Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000626 in 1,598,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AKAP7
NM_016377.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.896

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022915214).

BP6

Variant 6-131219726-A-G is Benign according to our data. Variant chr6-131219726-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3106398.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP7	NM_016377.4 linkuse as main transcript	c.768A>G	p.Ile256Met	missense_variant	7/8	ENST00000431975.7	NP_057461.2	Q9P0M2-1Q2TAJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP7	ENST00000431975.7 linkuse as main transcript	c.768A>G	p.Ile256Met	missense_variant	7/8	2	NM_016377.4	ENSP00000405252.2		Q9P0M2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152190

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:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240474

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000401

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:

0.00000553

AC:

AN:

1446004

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719774

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000181

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.52

DANN

Benign

0.66

DEOGEN2

Benign

0.0075

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.23

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.033

Sift

Benign

0.35

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0030

B;B

Vest4

0.12

MutPred

0.42

.;Loss of catalytic residue at I255 (P = 0.1298);

MVP

0.61

MPC

0.029

ClinPred

0.012

GERP RS

-4.7

Varity_R

0.27

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