rs397509408

Positions:

• chr17-40632336-T-TG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003079.5(SMARCE1):​c.572_573insC​(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

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]

ACMG classification

Verdict is Pathogenic. Variant got 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/exons	MANE	UniProt
SMARCE1	NM_003079.5	c.572_573insC	p.Ala192SerfsTer14	frameshift_variant	8/11	ENST00000348513.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCE1	ENST00000348513.12	c.572_573insC	p.Ala192SerfsTer14	frameshift_variant	8/11	1	NM_003079.5	P1

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

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs397509408; hg19: chr17-38788588;