chr22-23787178-GA-TT
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_003073.5(SMARCB1):c.9_10delinsTT(p.Met3_Met4delinsIleLeu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SMARCB1
NM_003073.5 missense
NM_003073.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.22
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a region_of_interest DNA-binding (size 112) in uniprot entity SNF5_HUMAN there are 13 pathogenic changes around while only 2 benign (87%) in NM_003073.5
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SMARCB1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.9_10delinsTT | p.Met3_Met4delinsIleLeu | missense_variant | 1/9 | ENST00000644036.2 | |
SMARCB1 | NM_001007468.3 | c.9_10delinsTT | p.Met3_Met4delinsIleLeu | missense_variant | 1/9 | ||
SMARCB1 | NM_001317946.2 | c.9_10delinsTT | p.Met3_Met4delinsIleLeu | missense_variant | 1/9 | ||
SMARCB1 | NM_001362877.2 | c.9_10delinsTT | p.Met3_Met4delinsIleLeu | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.9_10delinsTT | p.Met3_Met4delinsIleLeu | missense_variant | 1/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. This variant, c.9_10delinsTT, is a complex sequence change that results in the deletion of 2 and insertion of 2 amino acid(s) in the SMARCB1 protein (p.Met3_Met4delinsIleLeu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.