NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001532107.27

Allele description [Variation Report for NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp)]

NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp)

Gene:

AKT3:AKT serine/threonine kinase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q44

Genomic location:

Preferred name:

NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp)

HGVS:

NC_000001.11:g.243505296G>A
NG_029764.2:g.350784C>T
NM_001206729.2:c.1355-5510C>T
NM_001370074.1:c.1393C>T
NM_005465.7:c.1393C>TMANE SELECT
NM_005465.7:c.1393C>T
NM_181690.2:c.1355-5510C>T
NP_001357003.1:p.Arg465Trp
NP_005456.1:p.Arg465Trp
LRG_1396t1:c.1393C>T
LRG_1396:g.350784C>T
LRG_1396p1:p.Arg465Trp
NC_000001.10:g.243668598G>A
NM_005465.4:c.1393C>T
Q9Y243:p.Arg465Trp

Protein change:

R465W; ARG465TRP

Links:

UniProtKB: Q9Y243#VAR_069261; OMIM: 611223.0001; dbSNP: rs587776935

NCBI 1000 Genomes Browser:

rs587776935

Molecular consequence:

NM_001206729.2:c.1355-5510C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_181690.2:c.1355-5510C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001370074.1:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005465.7:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Microbe sample from Fomes fomentarius
Microbe sample from Fomes fomentarius

biosample
Adamtsl1 ADAMTS-like 1 [Rattus norvegicus]
Adamtsl1 ADAMTS-like 1 [Rattus norvegicus]
Gene ID:362539

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001747509	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Mar 1, 2021)	germline	clinical testing	Citation Link,
SCV002318995	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 17, 2022)	germline	clinical testing	Citation Link,
SCV005196923	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001747509

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Mar 1, 2021)

germline

clinical testing

Citation Link,

SCV002318995

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 17, 2022)

germline

clinical testing

Citation Link,

SCV005196923

Clinical Genetics Laboratory, Skane University Hospital Lund

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 27, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001747509.19

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneDx, SCV002318995.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate that R465W caused increased activity compared to wild-type AKT3 (Alcantara et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28475857, 28973083, 29286531, 32446860, 33942996, 33176815, 31785789, 22729224, 23592320, 25140959, 28969385)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005196923.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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