rs781775348
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_005751.5(AKAP9):āc.10220A>Cā(p.Glu3407Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,822 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E3407E) has been classified as Likely benign.
Frequency
Consequence
NM_005751.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.10220A>C | p.Glu3407Ala | missense_variant | 41/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.10196A>C | p.Glu3399Ala | missense_variant | 41/50 | ||
AKAP9 | NM_001379277.1 | c.4865A>C | p.Glu1622Ala | missense_variant | 20/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.10220A>C | p.Glu3407Ala | missense_variant | 41/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152266Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250272Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135492
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461556Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727078
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74406
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 527021). This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This variant is present in population databases (rs781775348, gnomAD 0.05%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 3407 of the AKAP9 protein (p.Glu3407Ala). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at