NM_152743.4(BRAT1):c.1594G>A (p.Gly532Arg) AND Rigidity and multifocal seizure syndrome, lethal neonatal

Clinical significance:Uncertain significance (Last evaluated: Jul 12, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_152743.4(BRAT1):c.1594G>A (p.Gly532Arg)]

NM_152743.4(BRAT1):c.1594G>A (p.Gly532Arg)

BRAT1:BRCA1 associated ATM activator 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_152743.4(BRAT1):c.1594G>A (p.Gly532Arg)
  • NC_000007.14:g.2539547C>T
  • NG_032167.1:g.21212G>A
  • NM_001350626.2:c.1594G>A
  • NM_001350627.2:c.1069G>A
  • NM_152743.4:c.1594G>AMANE SELECT
  • NP_001337555.1:p.Gly532Arg
  • NP_001337556.1:p.Gly357Arg
  • NP_689956.2:p.Gly532Arg
  • NC_000007.13:g.2579181C>T
  • NM_152743.3:c.1594G>A
  • NR_146879.2:n.1777G>A
Protein change:
dbSNP: rs142129866
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001350626.2:c.1594G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350627.2:c.1069G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152743.4:c.1594G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146879.2:n.1777G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL)
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)
SCV000652233Invitaecriteria provided, single submitter
Uncertain significance
(Jul 12, 2020)
germlineclinical testing

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

Summary from all submissions

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



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):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV000652233.5

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


This sequence change replaces glycine with arginine at codon 532 of the BRAT1 protein (p.Gly532Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs142129866, ExAC 0.1%). This variant has not been reported in the literature in individuals with BRAT1-related disease. ClinVar contains an entry for this variant (Variation ID: 472947). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.

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

Last Updated: Oct 8, 2021

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