NM_152743.4(BRAT1):c.1768C>T (p.Gln590Ter) AND Rigidity and multifocal seizure syndrome, lethal neonatal

Clinical significance:Pathogenic (Last evaluated: Jan 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001383083.1

Allele description [Variation Report for NM_152743.4(BRAT1):c.1768C>T (p.Gln590Ter)]

NM_152743.4(BRAT1):c.1768C>T (p.Gln590Ter)

Gene:
BRAT1:BRCA1 associated ATM activator 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.3
Genomic location:
Preferred name:
NM_152743.4(BRAT1):c.1768C>T (p.Gln590Ter)
HGVS:
  • NC_000007.14:g.2539181G>A
  • NG_032167.1:g.21578C>T
  • NM_001350626.2:c.1768C>T
  • NM_001350627.2:c.1243C>T
  • NM_152743.4:c.1768C>TMANE SELECT
  • NP_001337555.1:p.Gln590Ter
  • NP_001337556.1:p.Gln415Ter
  • NP_689956.2:p.Gln590Ter
  • NC_000007.13:g.2578815G>A
  • NR_146879.2:n.1951C>T
Protein change:
Q415*
Molecular consequence:
  • NR_146879.2:n.1951C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001350626.2:c.1768C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350627.2:c.1243C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_152743.4:c.1768C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL)
Identifiers:
MONDO: MONDO:0013784; MedGen: C3281029; Orphanet: 435845; OMIM: 614498

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001582104Invitaecriteria provided, single submitter
Pathogenic
(Jan 27, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

BRAT1-associated neurodegeneration: Intra-familial phenotypic differences in siblings.

Smith NJ, Lipsett J, Dibbens LM, Heron SE.

Am J Med Genet A. 2016 Nov;170(11):3033-3038. doi: 10.1002/ajmg.a.37853. Epub 2016 Aug 2.

PubMed [citation]
PMID:
27480663

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants.

Reuter MS, Walker S, Thiruvahindrapuram B, Whitney J, Cohn I, Sondheimer N, Yuen RKC, Trost B, Paton TA, Pereira SL, Herbrick JA, Wintle RF, Merico D, Howe J, MacDonald JR, Lu C, Nalpathamkalam T, Sung WWL, Wang Z, Patel RV, Pellecchia G, Wei J, et al.

CMAJ. 2018 Feb 5;190(5):E126-E136. doi: 10.1503/cmaj.171151.

PubMed [citation]
PMID:
29431110
PMCID:
PMC5798982
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001582104.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change results in a premature translational stop signal in the BRAT1 gene (p.Gln590*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 232 amino acids of the BRAT1 protein. This variant is present in population databases (rs746081291, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRAT1-related conditions. This variant disrupts the C-terminus of the BRAT1 protein. Other variant(s) that disrupt this region (p.Phe709Thrfs*17) have been determined to be pathogenic (PMID: 27480663, 29431110, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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