NM_213599.3(ANO5):c.1538C>T (p.Thr513Ile) AND not provided

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Nov 10, 2020
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:: RCV000487292.14

Allele description [Variation Report for NM_213599.3(ANO5):c.1538C>T (p.Thr513Ile)]

NM_213599.3(ANO5):c.1538C>T (p.Thr513Ile)

Gene:

ANO5:anoctamin 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p14.3

Genomic location:

Preferred name:

NM_213599.3(ANO5):c.1538C>T (p.Thr513Ile)

HGVS:

NC_000011.10:g.22259649C>T
NG_015844.1:g.71474C>T
NM_001142649.2:c.1535C>T
NM_213599.3:c.1538C>TMANE SELECT
NP_001136121.1:p.Thr512Ile
NP_998764.1:p.Thr513Ile
NP_998764.1:p.Thr513Ile
LRG_868t1:c.1538C>T
LRG_868:g.71474C>T
LRG_868p1:p.Thr513Ile
NC_000011.9:g.22281195C>T
NM_213599.2:c.1538C>T
Q75V66:p.Thr513Ile

Protein change:

T512I

Links:

UniProtKB: Q75V66#VAR_076477; dbSNP: rs281865467

NCBI 1000 Genomes Browser:

rs281865467

Molecular consequence:

NM_001142649.2:c.1535C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_213599.3:c.1538C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568781	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 10, 2020)	germline	clinical testing	Citation Link,
SCV002021400	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 7, 2019)	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

SCV000568781

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 10, 2020)

germline

clinical testing

Citation Link,

SCV002021400

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 7, 2019)

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	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 Eurofins Ntd Llc (ga), SCV000343086.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV000568781.4

#	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 T513I leads to phospholipid scrambling, suggesting a gain-of-function effect (Di Zanni et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32112655, 28176803, 27216912, 29175271, 29124309, 23047743)

#	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 Revvity Omics, Revvity, SCV002021400.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000343086	Eurofins Ntd Llc (ga)	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None (EGL Classification Definitions 2015)	Uncertain significance (Jun 19, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000343086

Eurofins Ntd Llc (ga)

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

(EGL Classification Definitions 2015)

Uncertain significance
(Jun 19, 2016)

germline

clinical testing

Citation Link

Last Updated: Sep 29, 2024

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