6-131281682-G-A

Variant summary

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

The NM_016377.4(AKAP7):​c.1003G>A​(p.Ala335Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,612,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AKAP7
NM_016377.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59
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]

Genome browser will be placed here

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=0.17076004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AKAP7NM_016377.4 linkuse as main transcriptc.1003G>A p.Ala335Thr missense_variant 8/8 ENST00000431975.7 NP_057461.2 Q9P0M2-1Q2TAJ5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AKAP7ENST00000431975.7 linkuse as main transcriptc.1003G>A p.Ala335Thr missense_variant 8/82 NM_016377.4 ENSP00000405252.2 Q9P0M2-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460530
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726530
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00000756

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 submitterclinical testingAmbry GeneticsOct 07, 2024The c.1003G>A (p.A335T) alteration is located in exon 8 (coding exon 8) of the AKAP7 gene. This alteration results from a G to A substitution at nucleotide position 1003, causing the alanine (A) at amino acid position 335 to be replaced by a threonine (T). 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
0.071
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0075
T;T;.;T
Eigen
Benign
-0.060
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.81
T;T;T;T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;.;.;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.35
N;N;N;N
REVEL
Benign
0.051
Sift
Benign
0.096
T;T;T;T
Sift4G
Benign
0.55
T;T;T;T
Polyphen
0.094
B;.;.;B
Vest4
0.16
MutPred
0.34
Gain of relative solvent accessibility (P = 0.0479);.;.;.;
MVP
0.52
MPC
0.030
ClinPred
0.39
T
GERP RS
6.0
Varity_R
0.050
gMVP
0.12

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.

Other links and lift over

dbSNP: rs1472192032; hg19: chr6-131602822; API