NM_003072.5(SMARCA4):c.778A>C (p.Met260Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 16, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV001026810.7

Allele description [Variation Report for NM_003072.5(SMARCA4):c.778A>C (p.Met260Leu)]

NM_003072.5(SMARCA4):c.778A>C (p.Met260Leu)

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.778A>C (p.Met260Leu)

HGVS:

NC_000019.10:g.10986922A>C
NG_011556.3:g.30991A>C
NM_001128844.3:c.778A>C
NM_001128845.2:c.778A>C
NM_001128846.2:c.778A>C
NM_001128847.4:c.778A>C
NM_001128848.2:c.778A>C
NM_001128849.3:c.778A>C
NM_001374457.1:c.778A>C
NM_001387283.1:c.778A>C
NM_003072.5:c.778A>CMANE SELECT
NP_001122316.1:p.Met260Leu
NP_001122317.1:p.Met260Leu
NP_001122318.1:p.Met260Leu
NP_001122319.1:p.Met260Leu
NP_001122320.1:p.Met260Leu
NP_001122321.1:p.Met260Leu
NP_001361386.1:p.Met260Leu
NP_001374212.1:p.Met260Leu
NP_003063.2:p.Met260Leu
LRG_878t1:c.778A>C
LRG_878:g.30991A>C
LRG_878p1:p.Met260Leu
NC_000019.9:g.11097598A>C
NG_011556.2:g.31001A>C
NM_001128849.1:c.778A>C
NR_164683.1:n.954A>C

Protein change:

M260L

Links:

dbSNP: rs1064795842

NCBI 1000 Genomes Browser:

rs1064795842

Molecular consequence:

NM_001128844.3:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128845.2:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128846.2:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128847.4:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128848.2:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128849.3:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374457.1:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001387283.1:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003072.5:c.778A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_164683.1:n.954A>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
SCV001189265	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Mar 4, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002535238	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Nov 16, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001189265

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Mar 4, 2021)

germline

clinical testing

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

Citation Link,

SCV002535238

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Nov 16, 2021)

germline

curation

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, curation

Citations

PubMed

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records.

He KY, Zhao Y, McPherson EW, Li Q, Xia F, Weng C, Wang K, He MM.

PLoS One. 2016;11(12):e0167847. doi: 10.1371/journal.pone.0167847.

PubMed [citation]

PMID:: 27930734
PMCID:: PMC5145192

Details of each submission

From Ambry Genetics, SCV001189265.4

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Sema4, Sema4, SCV002535238.1

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

#	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: Oct 20, 2024

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