NM_003072.5(SMARCA4):c.126G>C (p.Met42Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 13, 2021
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:: RCV000563791.3

Allele description [Variation Report for NM_003072.5(SMARCA4):c.126G>C (p.Met42Ile)]

NM_003072.5(SMARCA4):c.126G>C (p.Met42Ile)

Gene:

SMARCA4:SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_003072.5(SMARCA4):c.126G>C (p.Met42Ile)

HGVS:

NC_000019.10:g.10984277G>C
NG_011556.3:g.28346G>C
NM_001128844.3:c.126G>C
NM_001128845.2:c.126G>C
NM_001128846.2:c.126G>C
NM_001128847.4:c.126G>C
NM_001128848.2:c.126G>C
NM_001128849.3:c.126G>C
NM_001374457.1:c.126G>C
NM_001387283.1:c.126G>C
NM_003072.5:c.126G>CMANE SELECT
NP_001122316.1:p.Met42Ile
NP_001122317.1:p.Met42Ile
NP_001122318.1:p.Met42Ile
NP_001122319.1:p.Met42Ile
NP_001122320.1:p.Met42Ile
NP_001122321.1:p.Met42Ile
NP_001361386.1:p.Met42Ile
NP_001374212.1:p.Met42Ile
NP_003063.2:p.Met42Ile
LRG_878t1:c.126G>C
LRG_878:g.28346G>C
LRG_878p1:p.Met42Ile
NC_000019.9:g.11094953G>C
NG_011556.2:g.28356G>C
NM_001128849.1:c.126G>C
NR_164683.1:n.302G>C

Protein change:

M42I

Links:

dbSNP: rs765325777

NCBI 1000 Genomes Browser:

rs765325777

Molecular consequence:

NM_001128844.3:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128845.2:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128846.2:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128847.4:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128848.2:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128849.3:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374457.1:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001387283.1:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003072.5:c.126G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_164683.1:n.302G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000675184	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 13, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675184

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 13, 2021)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV000675184.5

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

Description

The p.M42I variant (also known as c.126G>C), located in coding exon 1 of the SMARCA4 gene, results from a G to C substitution at nucleotide position 126. The methionine at codon 42 is replaced by isoleucine, an amino acid with highly similar properties. Missense and in-frame variants in SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, the association of this alteration with Coffin-Siris syndrome is unknown; however, the association of this alteration with rhabdoid tumor predisposition syndrome is unlikely.

#	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 29, 2024

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