22-23787169-AATG-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM1PM4_SupportingBP6BS2
The NM_003073.5(SMARCB1):c.10_12delATG(p.Met4del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000243 in 1,602,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
SMARCB1
NM_003073.5 conservative_inframe_deletion
NM_003073.5 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.88
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 Likely_benign. Variant got -2 ACMG points.
PM1
In a region_of_interest DNA-binding (size 112) in uniprot entity SNF5_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_003073.5
PM4
Nonframeshift variant in NON repetitive region in NM_003073.5. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 22-23787169-AATG-A is Benign according to our data. Variant chr22-23787169-AATG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 532969.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS2
High AC in GnomAdExome4 at 38 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.10_12delATG | p.Met4del | conservative_inframe_deletion | Exon 1 of 9 | ENST00000644036.2 | NP_003064.2 | |
SMARCB1 | NM_001362877.2 | c.10_12delATG | p.Met4del | conservative_inframe_deletion | Exon 1 of 9 | NP_001349806.1 | ||
SMARCB1 | NM_001317946.2 | c.10_12delATG | p.Met4del | conservative_inframe_deletion | Exon 1 of 9 | NP_001304875.1 | ||
SMARCB1 | NM_001007468.3 | c.10_12delATG | p.Met4del | conservative_inframe_deletion | Exon 1 of 9 | NP_001007469.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000262 AC: 38AN: 1450158Hom.: 0 AF XY: 0.0000249 AC XY: 18AN XY: 721868
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74216
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 10, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 14, 2025 | This variant, c.10_12del, results in the deletion of 1 amino acid(s) of the SMARCB1 protein (p.Met4del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 532969). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at