NM_005591.4(MRE11):c.311G>C (p.Ser104Thr) AND Ataxia-telangiectasia-like disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 19, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000684797.6

Allele description

NM_005591.4(MRE11):c.311G>C (p.Ser104Thr)

Gene:

MRE11:MRE11 homolog, double strand break repair nuclease [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q21

Genomic location:

Preferred name:

NM_005591.4(MRE11):c.311G>C (p.Ser104Thr)

Other names:

p.S104T:AGT>ACT

HGVS:

NC_000011.10:g.94485927C>G
NG_007261.1:g.12948G>C
NM_001330347.2:c.311G>C
NM_005590.4:c.311G>C
NM_005591.4:c.311G>CMANE SELECT
NP_001317276.1:p.Ser104Thr
NP_005581.2:p.Ser104Thr
NP_005582.1:p.Ser104Thr
NP_005582.1:p.Ser104Thr
LRG_85t1:c.311G>C
LRG_85:g.12948G>C
LRG_85p1:p.Ser104Thr
NC_000011.9:g.94219093C>G
NM_005591.3:c.311G>C
p.S104T

Protein change:

S104T

Links:

dbSNP: rs587780140

NCBI 1000 Genomes Browser:

rs587780140

Molecular consequence:

NM_001330347.2:c.311G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005590.4:c.311G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005591.4:c.311G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ataxia-telangiectasia-like disorder (ATLD)
Identifiers:: MONDO: MONDO:0011457; MedGen: C1858391; OMIM: PS604391

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547395	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31780696, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547395

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 19, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Germline variants in cancer genes in high-risk non-BRCA patients from Puerto Rico.

Dutil J, Teer JK, Golubeva V, Yoder S, Tong WL, Arroyo N, Karam R, Echenique M, Matta JL, Monteiro AN.

Sci Rep. 2019 Nov 28;9(1):17769. doi: 10.1038/s41598-019-54170-6.

PubMed [citation]

PMID:: 31780696
PMCID:: PMC6882826

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000547395.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 104 of the MRE11 protein (p.Ser104Thr). This variant is present in population databases (rs587780140, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 31780696). ClinVar contains an entry for this variant (Variation ID: 127981). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Sep 16, 2024

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