rs768512576
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_005751.5(AKAP9):c.5825C>A(p.Thr1942Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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. T1942A) has been classified as Uncertain significance.
Frequency
Consequence
NM_005751.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.5825C>A | p.Thr1942Asn | missense_variant | 24/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.5825C>A | p.Thr1942Asn | missense_variant | 24/50 | ||
AKAP9 | NM_001379277.1 | c.470C>A | p.Thr157Asn | missense_variant | 3/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.5825C>A | p.Thr1942Asn | missense_variant | 24/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250986Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135624
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461546Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727070
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This variant is present in population databases (rs768512576, ExAC 0.002%). This sequence change replaces threonine with asparagine at codon 1942 of the AKAP9 protein (p.Thr1942Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2019 | The p.T1942N variant (also known as c.5825C>A), located in coding exon 24 of the AKAP9 gene, results from a C to A substitution at nucleotide position 5825. The threonine at codon 1942 is replaced by asparagine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at