rs397509408

Variant names:

• chr17-40632336-T-TG
• rs397509408
• NM_003079.5:c.572dupC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003079.5(SMARCE1):​c.572dupC​(p.Ala192SerfsTer14) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars). Synonymous variant affecting the same amino acid position (i.e. T191T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCE1 NM_003079.5 frameshift
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

Genes affected

SMARCE1 (HGNC:11109): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1) The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart. [provided by RefSeq, Jul 2008]

SMARCE1 Gene-Disease associations (from GenCC):

• familial meningioma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P, Ambry Genetics
• Coffin-Siris syndrome 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial multiple meningioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000264058 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCE1	NM_003079.5	c.572dupC	p.Ala192SerfsTer14	frameshift_variant	Exon 8 of 11	ENST00000348513.12	NP_003070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCE1	ENST00000348513.12	c.572dupC	p.Ala192SerfsTer14	frameshift_variant	Exon 8 of 11	1	NM_003079.5	ENSP00000323967.6
ENSG00000264058	ENST00000476049.1	n.*920dupC		non_coding_transcript_exon_variant	Exon 10 of 13	5		ENSP00000463483.1
ENSG00000264058	ENST00000476049.1	n.*920dupC		3_prime_UTR_variant	Exon 10 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial meningioma Other:1

Mar 01, 2013

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs397509408; hg19: chr17-38788588;