rs1555756326

Variant names:

• chr19-10989352-TTGA-T
• rs1555756326
• NM_001387283.1:c.1155_1157delTGA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_003072.5(SMARCA4):​c.1155_1157delTGA​(p.Glu386del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCA4 NM_003072.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.27

Genes affected

SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003072.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 19-10989352-TTGA-T is Pathogenic according to our data. Variant chr19-10989352-TTGA-T is described in ClinVar as [Pathogenic]. Clinvar id is 438797.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 8 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 7 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.1155_1157delTGA	p.Glu386del	disruptive_inframe_deletion	Exon 8 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.567_569delTGA	p.Glu190del	disruptive_inframe_deletion	Exon 4 of 32			ENSP00000496004.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Pathogenic:1

Apr 28, 2014

Donald Williams Parsons Laboratory, Baylor College of Medicine

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in this study in a 7-year-old male with neuroblastoma. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555756326; hg19: chr19-11100028;