Variant 6-131145356-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.91A>G(p.Thr31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000564 in 1,419,078 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: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

AKAP7
NM_016377.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

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:

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=0.047134012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4 linkuse as main transcript	c.91A>G	p.Thr31Ala	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.91A>G	p.Thr31Ala	missense_variant	2/8	2	NM_016377.4	P1	Q9P0M2-1
AKAP7	ENST00000683794.1 linkuse as main transcript	c.91A>G	p.Thr31Ala	missense_variant	2/8
AKAP7	ENST00000541650.5 linkuse as main transcript	c.88A>G	p.Thr30Ala	missense_variant	2/8	5
AKAP7	ENST00000366358.2 linkuse as main transcript	n.446A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

237736

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000672

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:

0.00

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.00000564

AC:

AN:

1419078

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

706220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000750

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:

0.00000460

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Feb 28, 2024

The c.91A>G (p.T31A) 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 91, causing the threonine (T) at amino acid position 31 to be replaced by an alanine (A). 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

0.065

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.76

Cadd

Benign

0.10

Dann

Benign

0.65

DEOGEN2

Benign

0.0076

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.11

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.015

Sift

Benign

0.41

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0

B;.

Vest4

0.034

MutPred

0.11

Gain of helix (P = 0.0425);.;

MVP

0.21

MPC

0.028

ClinPred

0.037

GERP RS

-1.6

Varity_R

0.024

gMVP

0.095

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