About SMARCB1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
SMARCB1 c.1091_1093del, p.(Lys364del)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
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Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 6
Benign evidence criteria: 0
Pathogenic criteria applied · 6
PS2Moderate
PS2 · moderate
A de novo occurrence of NM_003073.4:c.1091_1093del (p.Lys364del) with confirmed maternity and paternity was identified in one Coffin-Siris syndrome patient (subject 4) by Tsurusaki et al. 2012. Two additional CSS patients (subjects 21, 22) also harbor this variant but parental confirmation was not possible. One confirmed de novo in a disorder consistent with the variant's associated phenotype supports PS2 at moderate strength.
PS3Strong
PS3 · strong
Valencia et al. 2019 (PMID:31759698) directly tested the K364del variant in comprehensive functional assays. mSWI/SNF complexes containing K364del SMARCB1 exhibited significantly attenuated nucleosome remodeling activity and reduced ATPase activity on nucleosome substrates compared to wild-type. The K364del mutation completely disrupted SMARCB1 CTD binding to the nucleosome acidic patch. In SMARCB1-deficient MRT cell rescue experiments, K364del mutant complexes showed normal genome-wide targeting but substantially diminished DNA accessibility (ATAC-seq) and reduced nucleosome eviction (MNase-seq). Heterozygous K364del iPSCs demonstrated decreased DNA accessibility at pluripotency loci and impaired neuronal differentiation with significantly diminished neurite outgrowth, rescued by wild-type SMARCB1 restoration. The exact variant was directly tested with unequivocal deleterious functional effects across biochemical, genomic, and cellular differentiation assays.
PS4Strong
PS4 · strong
The p.Lys364del variant is the most recurrent SMARCB1 mutation in Coffin-Siris syndrome, identified in 9 independent CSS cases across published cohorts (Tsurusaki et al. 2012: 3 cases; Miyake et al. 2014: additional cases; Valencia et al. 2019: 9 total). The variant is essentially absent from population databases (gnomAD v4.1: 1/1,614,188 alleles, AF = 6.2e-07; gnomAD v2.1: absent). The extreme enrichment in affected individuals versus population controls meets PS4 at strong strength.
PM1Moderate
PM1 · moderate
The p.Lys364del variant is located in the SMARCB1 C-terminal domain (CTD; amino acids 357-377), a critical functional domain characterized by Valencia et al. 2019 as the nucleosome acidic patch binding domain. The CTD alpha-helix contains a dense cluster of basic residues required for mSWI/SNF complex-mediated nucleosome remodeling. This is a well-defined functional domain where missense and in-frame deletion mutations are enriched in both CSS and cancer, with no benign variation observed. PM1 is met at moderate strength based on the variant's location in this critical functional domain.
PM2Moderate
PM2 · moderate
The variant is essentially absent from large population databases. gnomAD v2.1: 0 alleles. gnomAD v4.1: 1 allele in 1,614,188 (AF = 6.2e-07, 0.000062%), well below the PM2 threshold of <0.1%. This extreme rarity in the general population supports PM2 at moderate strength.
PM4Moderate
PM4 · moderate
NM_003073.4:c.1091_1093del is an in-frame deletion of a single amino acid (p.Lys364del) in a non-repeat region of SMARCB1. The deletion removes a critical residue within the CTD nucleosome acidic patch binding domain, resulting in a protein length change with demonstrated functional consequences. PM4 is met at moderate strength.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Not classified
No source classification-combination explanation was recorded.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
1 / 1,614,188 alleles
gnomAD v4.1: 1 / 1,614,188 alleles. Recorded AF 6.19507e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
8 reported laboratory submissions
8 Pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
In progress — evidence not uploaded yet.
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 6 met · 9 not met · 0 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_003073.4:c.1091_1093del (p.Lys364del) is an in-frame deletion in exon 8 of SMARCB1, removing a single lysine residue from the C-terminal domain alpha-helix.
The variant has been identified in 9 independent individuals with Coffin-Siris syndrome, a rare autosomal dominant neurodevelopmental disorder characterized by intellectual disability, coarse facial features, and hypoplastic fifth digit nails.
One confirmed de novo occurrence with both maternity and paternity confirmed has been reported in a CSS patient.
The variant is essentially absent from large population databases (gnomAD v4.1: 1/1,614,188 alleles; gnomAD v2.1: absent), consistent with a rare pathogenic variant.
Comprehensive functional studies by Valencia et al. (2019) directly demonstrated that the K364del variant disrupts SMARCB1 C-terminal domain binding to the nucleosome acidic patch, significantly attenuates mSWI/SNF complex nucleosome remodeling and ATPase activity, and impairs genome-wide DNA accessibility.
In iPSC-derived neuronal differentiation models, heterozygous K364del resulted in significantly diminished neurite outgrowth and reduced neuron counts, with phenotypic rescue upon restoration of wild-type SMARCB1, establishing a direct causal link between this variant and neurodevelopmental deficits.
Residue K364 is located within the SMARCB1 C-terminal alpha-helical domain (aa 357-377), a well-characterized functional domain that directly binds the nucleosome acidic patch and is essential for mSWI/SNF-mediated chromatin remodeling. This domain is a hotspot for CSS-associated mutations with no benign variation.
The variant is classified as Pathogenic in ClinVar (Variation ID: 30201) by 8 clinical laboratories; however, the aggregate review status is 'criteria provided, single submitter' (1-star), which does not meet the 3-star threshold for PP5 application.
Applying generic ACMG/AMP 2015 criteria: 2 strong (PS3, PS4), 4 moderate (PS2, PM1, PM2, PM4) pathogenic criteria are met. No benign criteria are met. This combination exceeds the threshold for Pathogenic classification (requires 2 strong OR 1 strong + ≥3 moderate).
No criteria match.
Met · 6
PS2 ModerateA de novo occurrence of NM_003073.4:c.1091_1093del (p.Lys364del) with confirmed maternity and paternity was identified in one Coffin-Siris syndrome patient (subject 4) by Tsurusaki et al. 2012. Two additional CSS patients (subjects 21, 22) also harbor this variant but parental confirmation was not possible. One confirmed de novo in a disorder consistent with the variant's associated phenotype supports PS2 at moderate strength. Details ▾Hide ▴
Evidence considered
- Subject 4: confirmed de novo p.Lys364del in CSS patient with both parental samples tested negative
- Subjects 21 and 22: same variant but parental samples unavailable for de novo confirmation
- Control frequency 0/502 Japanese alleles
Still missing
- Additional confirmed de novo observations would strengthen to PS2_strong
Sources
PS3 StrongValencia et al. 2019 (PMID:31759698) directly tested the K364del variant in comprehensive functional assays. mSWI/SNF complexes containing K364del SMARCB1 exhibited significantly attenuated nucleosome remodeling activity and reduced ATPase activity on nucleosome substrates compared to wild-type. The K364del mutation completely disrupted SMARCB1 CTD binding to the nucleosome acidic patch. In SMARCB1-deficient MRT cell rescue experiments, K364del mutant complexes showed normal genome-wide targeting but substantially diminished DNA accessibility (ATAC-seq) and reduced nucleosome eviction (MNase-seq). Heterozygous K364del iPSCs demonstrated decreased DNA accessibility at pluripotency loci and impaired neuronal differentiation with significantly diminished neurite outgrowth, rescued by wild-type SMARCB1 restoration. The exact variant was directly tested with unequivocal deleterious functional effects across biochemical, genomic, and cellular differentiation assays. Details ▾Hide ▴
Evidence considered
- Nucleosome remodeling (REAA): K364del mSWI/SNF complexes show significant attenuation of remodeling activity
- ATPase activity: significantly reduced on nucleosome substrates but not on free DNA
- CTD-nucleosome binding: K364del completely abrogates SMARCB1 CTD binding to mononucleosomes
- Genome-wide: K364del complexes target normally but fail to generate DNA accessibility (ATAC-seq
- MNase-seq)
- iPSC neuronal differentiation: heterozygous K364del iPSCs show diminished neurite outgrowth and neuron counts
- rescued by WT SMARCB1
- NMR structure: K364del disrupts helical register of the basic charge cluster in the CTD alpha-helix
Sources
PS4 StrongThe p.Lys364del variant is the most recurrent SMARCB1 mutation in Coffin-Siris syndrome, identified in 9 independent CSS cases across published cohorts (Tsurusaki et al. 2012: 3 cases; Miyake et al. 2014: additional cases; Valencia et al. 2019: 9 total). The variant is essentially absent from population databases (gnomAD v4.1: 1/1,614,188 alleles, AF = 6.2e-07; gnomAD v2.1: absent). The extreme enrichment in affected individuals versus population controls meets PS4 at strong strength. Details ▾Hide ▴
Evidence considered
- 9 independent CSS cases with p.Lys364del across published studies
- gnomAD v2.1: absent
- gnomAD v4.1: 1 allele in 1
- 614
- 188 (AF = 6.2e-07)
- Absent from 502 Japanese controls (Tsurusaki et al. 2012)
Sources
PM1 ModerateThe p.Lys364del variant is located in the SMARCB1 C-terminal domain (CTD; amino acids 357-377), a critical functional domain characterized by Valencia et al. 2019 as the nucleosome acidic patch binding domain. The CTD alpha-helix contains a dense cluster of basic residues required for mSWI/SNF complex-mediated nucleosome remodeling. This is a well-defined functional domain where missense and in-frame deletion mutations are enriched in both CSS and cancer, with no benign variation observed. PM1 is met at moderate strength based on the variant's location in this critical functional domain. Details ▾Hide ▴
Evidence considered
- K364 is within the CTD alpha-helix (aa 357-377)
- the nucleosome acidic patch binding domain
- CTD is a well-characterized functional domain required for mSWI/SNF remodeling activity
- Multiple CSS-associated missense mutations cluster in this domain (R377H
- K363N
- R366C
- R374Q)
- No benign variation observed in this domain
Sources
PM2 ModerateThe variant is essentially absent from large population databases. gnomAD v2.1: 0 alleles. gnomAD v4.1: 1 allele in 1,614,188 (AF = 6.2e-07, 0.000062%), well below the PM2 threshold of <0.1%. This extreme rarity in the general population supports PM2 at moderate strength. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (0 alleles)
- gnomAD v4.1: 1/1
- 614
- 188 alleles (AF = 6.2e-07)
- gnomAD-Canada v1.0: absent
- Highest subpopulation AF: European (non-Finnish) = 8.5e-07
Sources
PM4 ModerateNM_003073.4:c.1091_1093del is an in-frame deletion of a single amino acid (p.Lys364del) in a non-repeat region of SMARCB1. The deletion removes a critical residue within the CTD nucleosome acidic patch binding domain, resulting in a protein length change with demonstrated functional consequences. PM4 is met at moderate strength. Details ▾Hide ▴
Evidence considered
- In-frame single amino acid deletion (K364del) in exon 8
- Residue is in a non-repeat
- functionally critical region (CTD alpha-helix)
- Removal of K364 disrupts the basic charge cluster required for nucleosome acidic patch binding
Sources
Not met · 9 · evaluated, threshold not reached
PP3 In silico pathogenicity prediction tools (REVEL, BayesDel) are not applicable for in-frame deletions and were not computed for this variant. SpliceAI predicts no significant splicing impact (max delta score = 0.00). No HCI prior score is available for SMARCB1. There is no computational evidence to support PP3. Details ▾Hide ▴
Evidence considered
- REVEL/BayesDel: not applicable (in-frame deletion
- not SNV)
- SpliceAI: max delta = 0.00
- no predicted splice impact
- HCI prior: not available for SMARCB1
Sources
PP4 While patients with this variant present with classical Coffin-Siris syndrome features (severe intellectual disability, coarse facies, hypoplastic fifth digit nails), CSS is genetically heterogeneous — caused by mutations in at least six different BAF complex genes (SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A, ARID1B). The phenotype is not highly specific for a single genetic etiology, and PP4 is therefore not met. Details ▾Hide ▴
Evidence considered
- Patients exhibit classical CSS features: severe ID
- coarse facies
- digital/nail hypoplasia
- CSS is genetically heterogeneous — caused by mutations in multiple BAF complex genes
- Phenotype alone cannot distinguish SMARCB1-CSS from other BAF-related CSS
Sources
PP5 While ClinVar classifies this variant as Pathogenic (Variation ID: 30201) with submissions from 8 clinical laboratories, the aggregate review status is 'criteria provided, single submitter' (1-star). PP5 requires ClinVar 3-star expert panel review to be applied at supporting strength. The current review status does not meet the 3-star threshold for PP5. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 30201: classified as Pathogenic by 8 clinical laboratories
- Review status: 'criteria provided
- single submitter' (1-star)
- No expert panel review (3-star) available
Sources
BA1 The variant has an allele frequency of 6.2e-07 (0.000062%) in gnomAD v4.1, far below the BA1 threshold of >5%. BA1 is not met. Details ▾Hide ▴
BS1 The variant has an allele frequency of 6.2e-07 (0.000062%) in gnomAD v4.1, far below the BS1 threshold of >0.3% for a dominant disorder. BS1 is not met. Details ▾Hide ▴
BS2 A single allele is observed in gnomAD v4.1 (1/1,614,188). CSS is a severe pediatric-onset dominant disorder with full penetrance expected early in life. The single observation may represent a mosaic carrier, technical artifact, or an individual with subclinical features. A single observation in a population database that screens out severe pediatric disease does not constitute sufficient evidence for BS2. Details ▾Hide ▴
Evidence considered
- 1 allele in gnomAD v4.1 (1
- 614
- 188 total alleles)
- CSS is a severe early-onset dominant disorder
- healthy adult carriers are not expected
Still missing
- Phenotype of the single gnomAD v4.1 carrier is unknown
Sources
BS3 Well-established functional studies (Valencia et al. 2019) demonstrate that K364del has a damaging effect on SMARCB1 function — disrupting nucleosome acidic patch binding, reducing chromatin remodeling activity, and impairing neuronal differentiation. BS3 requires functional studies showing no damaging effect; the available evidence demonstrates the opposite. Details ▾Hide ▴
Evidence considered
- K364del disrupts SMARCB1 CTD-nucleosome acidic patch binding
- Reduces mSWI/SNF remodeling and ATPase activity on nucleosome substrates
- Impairs DNA accessibility and neuronal differentiation in iPSC models
Sources
BP3 BP3 applies to in-frame deletions in repetitive regions without known function. The K364del deletion occurs in the SMARCB1 C-terminal alpha-helical domain, which is a well-characterized functional domain (nucleosome acidic patch binding region). This is not a repetitive region without function. BP3 is not met. Details ▾Hide ▴
Evidence considered
- K364 is in the CTD alpha-helix
- a well-characterized functional domain
- CTD has established function in nucleosome acidic patch binding and chromatin remodeling
Sources
BP4 Computational predictors (REVEL, BayesDel) are not applicable for in-frame deletions. SpliceAI predicts no splicing impact (max delta = 0.00), which is neutral but does not constitute positive evidence for a benign effect on protein function. There is no computational evidence suggesting the variant is benign; BP4 is not met. Details ▾Hide ▴
Evidence considered
- REVEL/BayesDel: not applicable (in-frame deletion
- not SNV)
- SpliceAI: no splicing impact predicted (neutral
- not benign-supporting)
- No in silico evidence for benign effect
Sources
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_003073.4:c.1091_1093del is an in-frame deletion (p.Lys364del) that does not fall into the default PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus). The variant does not trigger nonsense-mediated decay. Published literature indicates SMARCB1 mutations in Coffin-Siris syndrome exert dominant-negative or gain-of-function effects, excluding haploinsufficiency as the disease mechanism (Tsurusaki et al. 2012). PVS1 is not applicable for this non-null variant with a dominant-negative mechanism. Details ▾Hide ▴
Evidence considered
- In-frame deletion of a single amino acid (K364) in exon 8 of 9
- Does not trigger NMD
- protein product is stable and incorporates into mSWI/SNF complexes
- SMARCB1 CSS mutations are non-truncating and exert dominant-negative effects
- not haploinsufficiency
Sources
PS1 N/APS1 applies to nucleotide substitutions where a different nucleotide change at the same position has been established as pathogenic. This is an in-frame deletion, not a nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
PM3 N/APM3 applies to recessive disorders. Coffin-Siris syndrome is an autosomal dominant disorder; PM3 is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 requires a novel missense change at an amino acid residue where a different pathogenic missense change has been previously identified. This variant is an in-frame deletion, not a missense substitution. Additionally, PM5 candidate harvesting was unable to identify same-residue comparator missense variants with confirmed pathogenic classifications. PM5 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is an in-frame deletion (p.Lys364del)
- not a missense change
- No same-residue pathogenic missense comparators identified
PM6 N/APM6 applies to de novo observations without confirmed maternity and paternity. One de novo occurrence with confirmed parentage has already been applied as PS2 (moderate). The additional cases without parental confirmation (subjects 21, 22 in Tsurusaki et al. 2012) cannot be separately counted without double-counting the de novo evidence. PM6 is not applied to avoid evidence double-counting. Details ▾Hide ▴
No further detail was recorded.
PP1 N/APP1 requires cosegregation data in multiple affected family members. No family segregation data is available in the provided evidence. Coffin-Siris syndrome cases with this variant are sporadic with de novo occurrence. Details ▾Hide ▴
No further detail was recorded.
PP2 N/APP2 applies specifically to missense variants in genes with a low rate of benign missense variation. This is an in-frame deletion, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BS4 N/ABS4 requires lack of segregation in affected family members. No family segregation data is available; all reported cases are sporadic de novo occurrences. Details ▾Hide ▴
No further detail was recorded.
BP1 N/ABP1 applies specifically to missense variants in genes where primarily truncating variants cause disease. This is an in-frame deletion, not a missense variant. Additionally, SMARCB1 CSS-associated mutations are non-truncating, so BP1 is not applicable. Details ▾Hide ▴
No further detail was recorded.
BP2 N/ABP2 requires observation of the variant in trans with a pathogenic variant for a fully penetrant dominant disorder. CSS is dominant and all reported cases are heterozygous; no trans configuration data exists or is expected. Details ▾Hide ▴
No further detail was recorded.
BP5 N/ABP5 requires the variant to be found in a case with an alternative molecular basis for disease. No such data is available for this variant. Details ▾Hide ▴
No further detail was recorded.
BP6 N/ABP6 requires a reputable source to report the variant as benign. ClinVar classifies this variant as Pathogenic (Variation ID: 30201). BP6 is not applicable. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. This is an in-frame deletion, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is intended for situations where a reputable source reports the variant as pathogenic but the evaluating laboratory lacks access to the primary evidence. The evidence for this variant is directly available and has been independently evaluated; PS5 is not applicable. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- SMARCB1
- Transcript
- NM_003073.4
- Coding (HGVS c.)
- NM_003073.4:c.1091_1093del
- Protein (HGVS p.)
- NP_003064.2:p.(Lys364del)
- GRCh38
- chr22:23833669 GAGA>G
- GRCh37
- chr22:24175856 GAGA>G
- ClinVar
- 30201
Gene diagram
Every interpreted variant in SMARCB1, mapped onto the exon structure of NM_003073.4. Select a row to find it on the plot.
SMARCB1NM_003073.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in SMARCB1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
1 / 1,614,188 alleles
AF 6.2e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,614,188 alleles · 0 hom
| European (non-Finnish)1 / 1,180,040 | 8.5e-07 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19507e-07; MAF= 0.00006%, 1/1614188 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47429e-07; MAF= 0.00008%, 1/1180040 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 In silico pathogenicity prediction tools (REVEL, BayesDel) are not applicable for in-frame deletions and were not computed for this variant. SpliceAI predicts no significant splicing impact (max delta score = 0.00). No HCI prior score is available for SMARCB1. There is no computational evidence to support PP3. Details ▾Hide ▴
Evidence considered
- REVEL/BayesDel: not applicable (in-frame deletion
- not SNV)
- SpliceAI: max delta = 0.00
- no predicted splice impact
- HCI prior: not available for SMARCB1
Sources
BP4 Computational predictors (REVEL, BayesDel) are not applicable for in-frame deletions. SpliceAI predicts no splicing impact (max delta = 0.00), which is neutral but does not constitute positive evidence for a benign effect on protein function. There is no computational evidence suggesting the variant is benign; BP4 is not met. Details ▾Hide ▴
Evidence considered
- REVEL/BayesDel: not applicable (in-frame deletion
- not SNV)
- SpliceAI: no splicing impact predicted (neutral
- not benign-supporting)
- No in silico evidence for benign effect
Sources
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. This is an in-frame deletion, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
In progress — evidence not uploaded yet.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 28481359 ↗Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients.No paper-specific finding is recorded.
-
PMID 31759698 ↗Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling.Valencia AM et al. · 2019No paper-specific finding is recorded.
-
PMID 22426308 ↗Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.Tsurusaki Y et al. · 2012No paper-specific finding is recorded.
-
PMID 23815551 ↗Coffin-Siris syndrome is a SWI/SNF complex disorder.Tsurusaki Y et al. · 2014No paper-specific finding is recorded.
-
PMID 25081545 ↗Numerous BAF complex genes are mutated in Coffin-Siris syndrome.Miyake N et al. · 2014No paper-specific finding is recorded.
-
PMID 25168959 ↗Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A.Kosho T et al. · 2014No paper-specific finding is recorded.
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PMID 35101336 ↗Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).No paper-specific finding is recorded.
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PMID 23637025 ↗Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature.Kosho T et al. · 2013No paper-specific finding is recorded.
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PMID 23619274 ↗American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,614,188 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
8 Pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_003073.4%3Ac.1091_1093del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/22-24175856-GAGA-G?dataset=gn…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr22-23833669-GAGA-G?dataset…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/22-23833669-GAGA-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_003073.4%3Ac.1091…
- OncoKB ↗www.oncokb.org/gene/SMARCB1/K364del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=SMARCB1+c.1091_1093del
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19507e-07; MAF= 0.00006%, 1/1614188 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47429e-07; MAF= 0.00008%, 1/1180040 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
In progress — evidence not uploaded yet.
In silico
In progress — evidence not uploaded yet.
Functional
In progress — evidence not uploaded yet.
Somatic
In progress — evidence not uploaded yet.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Literature
In progress — evidence not uploaded yet.