VCV000136347.43 - ClinVar

NM_005751.5(AKAP9):c.1389G>T (p.Met463Ile)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign

11 out of 14 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005751.5(AKAP9):c.1389G>T (p.Met463Ile)

Variation ID: 136347 Accession: VCV000136347.43

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q21.2 7: 92001306 (GRCh38) [ NCBI UCSC ] 7: 91630620 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 14, 2015	Feb 15, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_005751.5:c.1389G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005742.4:p.Met463Ile	missense
NM_147185.3:c.1389G>T	NP_671714.1:p.Met463Ile	missense
NC_000007.14:g.92001306G>T
NC_000007.13:g.91630620G>T
NG_011623.1:g.65432G>T
LRG_331:g.65432G>T
LRG_331t1:c.1389G>T	LRG_331p1:p.Met463Ile

... more HGVS ... less HGVS

Protein change

M463I

Other names

p.M463I:ATG>ATT

Canonical SPDI

NC_000007.14:92001305:G:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.37220 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.37220

1000 Genomes Project 30x 0.37539

The Genome Aggregation Database (gnomAD), exomes 0.37814

Exome Aggregation Consortium (ExAC) 0.38290

The Genome Aggregation Database (gnomAD), exomes 0.38631

The Genome Aggregation Database (gnomAD) 0.41484

Trans-Omics for Precision Medicine (TOPMed) 0.41577

The Genome Aggregation Database (gnomAD) 0.41920

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.44047

Links

ClinGen: CA163163 dbSNP: rs6964587 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
AKAP9		-	-	GRCh38 GRCh37	3612	3740

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (7)	criteria provided, multiple submitters, no conflicts	Aug 12, 2019	RCV000123592.22
Colorectal cancer	Benign (1)	criteria provided, single submitter	Jun 24, 2013	RCV000171778.3
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Mar 23, 2015	RCV000244317.3
Long QT syndrome	Benign (1)	criteria provided, single submitter	Feb 4, 2026	RCV000350947.12
Long QT syndrome 11	Benign (3)	criteria provided, multiple submitters, no conflicts	Nov 29, 2023	RCV000602690.15
not provided	Benign (1)	criteria provided, single submitter	-	RCV004712080.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Jun 24, 2013) C Contributing to aggregate classification	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Colorectal cancer	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000050789.2 First in ClinVar: Jun 04, 2015 Last updated: Sep 14, 2015 Comments (2): Medical sequencing The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)	Observation: 1 Collection method: research Allele origin: unknown Affected status: unknown more Observation 1 Collection method: research Allele origin: unknown Affected status: unknown Number of individuals with the variant: 543 Platform type: next-gen sequencing

Benign (Dec 05, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Long QT syndrome 11	Genome-Nilou Lab Accession: SCV002524818.1 First in ClinVar: Jun 10, 2022 Last updated: Jun 10, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Nov 29, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Long QT syndrome 11	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001156896.6 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 25, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538267.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Comment: show Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 5727/13002=44% (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Method: Genome/Exome Filtration

Benign (Aug 08, 2011) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000166931.12 First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Mar 23, 2015) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV000317558.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: show This alteration is classified as 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (May 19, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not specified	Eurofins Ntd Llc (ga) Accession: SCV000232692.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AKAP9 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 13 Zygosity: 5 Homozygotes, 8 Single Heterozygotes Sex: mixed

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Long QT syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000263.8 First in ClinVar: Dec 17, 2019 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000311253.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Aug 12, 2019) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001361192.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020	Comment: show Variant summary: AKAP9 c.1389G>T (p.Met463Ile) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.38 in 250610 control chromosomes, predominantly at a frequency of 0.51 within the African or African-American subpopulation in the gnomAD database, including 2115 homozygotes. Therefore, suggesting the variant is the major allele found in population(s) of African American origin. Four ClinVar submissions (evaluation after 2014) cite the variant three times as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal dominant inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005266346.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Clinical Genetics, Academic Medical Center Study: VKGL Data-share Consensus Accession: SCV001924686.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Study: VKGL Data-share Consensus Accession: SCV001958696.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	Long QT syndrome 11	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734574.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 5727/13002=44%

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This alteration is classified as 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.

Comment:

Variant summary: AKAP9 c.1389G>T (p.Met463Ile) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.38 in 250610 control chromosomes, predominantly at a frequency of 0.51 within the African or African-American subpopulation in the gnomAD database, including 2115 homozygotes. Therefore, suggesting the variant is the major allele found in population(s) of African American origin. Four ClinVar submissions (evaluation after 2014) cite the variant three times as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AKAP9	-	-	-	-

Text-mined citations for rs6964587 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026