chr7-92085619-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005751.5(AKAP9):c.8957C>T(p.Ala2986Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,632 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A2986A) has been classified as Likely benign.
Frequency
Consequence
NM_005751.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.8957C>T | p.Ala2986Val | missense_variant | 36/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.8933C>T | p.Ala2978Val | missense_variant | 36/50 | ||
AKAP9 | NM_001379277.1 | c.3602C>T | p.Ala1201Val | missense_variant | 15/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.8957C>T | p.Ala2986Val | missense_variant | 36/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152036Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250994Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135648
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461632Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727134
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74236
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 648434). This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This variant is present in population databases (rs763275190, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2986 of the AKAP9 protein (p.Ala2986Val). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2023 | The c.8957C>T (p.A2986V) alteration is located in exon 36 (coding exon 36) of the AKAP9 gene. This alteration results from a C to T substitution at nucleotide position 8957, causing the alanine (A) at amino acid position 2986 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at