chr22-23803382-TG-T

Position:

• chr22-23803382-TG-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_003073.5(SMARCB1):​c.591del​(p.Gln198ArgfsTer11) variant causes a frameshift 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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SMARCB1 NM_003073.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.96

Genes affected

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Pathogenic. Variant got 11 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
• PP5: Variant 22-23803382-TG-T is Pathogenic according to our data. Variant chr22-23803382-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 8024.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCB1	NM_003073.5	c.591del	p.Gln198ArgfsTer11	frameshift_variant	5/9	ENST00000644036.2	NP_003064.2
SMARCB1	NM_001362877.2	c.645del	p.Gln216ArgfsTer11	frameshift_variant	5/9		NP_001349806.1
SMARCB1	NM_001317946.2	c.618del	p.Gln207ArgfsTer11	frameshift_variant	5/9		NP_001304875.1
SMARCB1	NM_001007468.3	c.564del	p.Gln189ArgfsTer11	frameshift_variant	5/9		NP_001007469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2	c.591del	p.Gln198ArgfsTer11	frameshift_variant	5/9		NM_003073.5	ENSP00000494049	A1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs587776678; hg19: chr22-24145569;