rs780099038
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005751.5(AKAP9):c.9136C>T(p.Arg3046Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,808 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3046Q) has been classified as Likely benign.
Frequency
Consequence
NM_005751.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.9136C>T | p.Arg3046Trp | missense_variant | 37/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.9112C>T | p.Arg3038Trp | missense_variant | 37/50 | ||
AKAP9 | NM_001379277.1 | c.3781C>T | p.Arg1261Trp | missense_variant | 16/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.9136C>T | p.Arg3046Trp | missense_variant | 37/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251370Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135848
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461796Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727202
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2021 | This sequence change replaces arginine with tryptophan at codon 3046 of the AKAP9 protein (p.Arg3046Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs780099038, ExAC 0.003%). This variant has not been reported in the literature in individuals with AKAP9-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at