rs140470576
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_005751.5(AKAP9):c.10118C>A(p.Ser3373Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,180 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3373C) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKAP9 | NM_005751.5 | c.10118C>A | p.Ser3373Tyr | missense_variant | 41/50 | ENST00000356239.8 | |
AKAP9 | NM_147185.3 | c.10094C>A | p.Ser3365Tyr | missense_variant | 41/50 | ||
AKAP9 | NM_001379277.1 | c.4763C>A | p.Ser1588Tyr | missense_variant | 20/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKAP9 | ENST00000356239.8 | c.10118C>A | p.Ser3373Tyr | missense_variant | 41/50 | 1 | NM_005751.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000736 AC: 112AN: 152190Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00136 AC: 342AN: 251222Hom.: 4 AF XY: 0.00177 AC XY: 240AN XY: 135806
GnomAD4 exome AF: 0.00150 AC: 2198AN: 1461872Hom.: 12 Cov.: 33 AF XY: 0.00169 AC XY: 1229AN XY: 727234
GnomAD4 genome AF: 0.000742 AC: 113AN: 152308Hom.: 2 Cov.: 32 AF XY: 0.000752 AC XY: 56AN XY: 74472
ClinVar
Submissions by phenotype
not provided Benign:6
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | AKAP9: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Long QT syndrome Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Uncertain significance, criteria provided, single submitter | research | Dept of Medical Biology, Uskudar University | Jan 08, 2024 | Criteria: BS1 - |
Long QT syndrome 11 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Dec 16, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 14, 2023 | - - |
Congenital long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 06, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 01, 2019 | 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