NM_000051.4(ATM):c.4196C>G (p.Thr1399Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 3, 2021
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:: RCV000486909.12

Allele description [Variation Report for NM_000051.4(ATM):c.4196C>G (p.Thr1399Ser)]

NM_000051.4(ATM):c.4196C>G (p.Thr1399Ser)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.4196C>G (p.Thr1399Ser)

HGVS:

NC_000011.10:g.108289063C>G
NG_009830.1:g.71232C>G
NM_000051.4:c.4196C>GMANE SELECT
NM_001351834.2:c.4196C>G
NP_000042.3:p.Thr1399Ser
NP_000042.3:p.Thr1399Ser
NP_001338763.1:p.Thr1399Ser
LRG_135t1:c.4196C>G
LRG_135:g.71232C>G
LRG_135p1:p.Thr1399Ser
NC_000011.9:g.108159790C>G
NM_000051.3:c.4196C>G

Protein change:

T1399S

Links:

dbSNP: rs786203761

NCBI 1000 Genomes Browser:

rs786203761

Molecular consequence:

NM_000051.4:c.4196C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.4196C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000564639	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 10, 2018)	germline	clinical testing	Citation Link,
SCV002010817	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2021)	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

SCV000564639

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 10, 2018)

germline

clinical testing

Citation Link,

SCV002010817

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 2021)

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	not provided	not provided	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 GeneDx, SCV000564639.3

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

Description

This variant is denoted ATM c.4196C>G at the cDNA level, p.Thr1399Ser (T1399S) at the protein level, and results in the change of a Threonine to a Serine (ACC>AGC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. ATM Thr1399Ser was not observed in large population cohorts (Lek 2016). This variant is not located within a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Thr1399Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

#	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 Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002010817.3

#	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	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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