rs752626437
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005751.5(AKAP9):āc.1253T>Cā(p.Ile418Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005751.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.1253T>C | p.Ile418Thr | missense_variant | 8/50 | ENST00000356239.8 | NP_005742.4 | |
AKAP9 | NM_147185.3 | c.1253T>C | p.Ile418Thr | missense_variant | 8/50 | NP_671714.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.1253T>C | p.Ile418Thr | missense_variant | 8/50 | 1 | NM_005751.5 | ENSP00000348573.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250420Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135512
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461754Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727174
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 07, 2017 | This variant is present in population databases (rs752626437, ExAC 0.009%). This sequence change replaces isoleucine with threonine at codon 418 of the AKAP9 protein (p.Ile418Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant has not been reported in the literature in individuals with a AKAP9-related disease. In summary, this variant has uncertain impact on AKAP9 function. The available evidence is currently insufficient to determine its role 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at