rs1056057044
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_003072.5(SMARCA4):c.290G>A(p.Gly97Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SMARCA4
NM_003072.5 missense
NM_003072.5 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 3.78
Genes affected
SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the SMARCA4 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 59 curated pathogenic missense variants (we use a threshold of 10). The gene has 56 curated benign missense variants. Gene score misZ: 6.8459 (above the threshold of 3.09). Trascript score misZ: 8.7957 (above the threshold of 3.09). GenCC associations: The gene is linked to uterine corpus sarcoma, Coffin-Siris syndrome 1, intellectual disability, autosomal dominant 16, rhabdoid tumor predisposition syndrome 2, familial rhabdoid tumor, hereditary nonpolyposis colon cancer, Coffin-Siris syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.2976352).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SMARCA4 | ENST00000646693.2 | c.290G>A | p.Gly97Glu | missense_variant | Exon 3 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
| SMARCA4 | ENST00000344626.10 | c.290G>A | p.Gly97Glu | missense_variant | Exon 3 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
| SMARCA4 | ENST00000643549.1 | c.290G>A | p.Gly97Glu | missense_variant | Exon 3 of 35 | ENSP00000493975.1 | ||||
| SMARCA4 | ENST00000541122.6 | c.290G>A | p.Gly97Glu | missense_variant | Exon 4 of 35 | 5 | ENSP00000445036.2 | |||
| SMARCA4 | ENST00000643296.1 | c.290G>A | p.Gly97Glu | missense_variant | Exon 3 of 34 | ENSP00000496635.1 | ||||
| SMARCA4 | ENST00000644737.1 | c.290G>A | p.Gly97Glu | missense_variant | Exon 3 of 34 | ENSP00000495548.1 | ||||
| SMARCA4 | ENST00000589677.5 | c.290G>A | p.Gly97Glu | missense_variant | Exon 4 of 35 | 5 | ENSP00000464778.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Sep 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The p.G97E variant (also known as c.290G>A), located in coding exon 2 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 290. The glycine at codon 97 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;.;.;.;.;D;.;.;.;D;D;.;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.;.;.;N;N;.;N;N;N;N;.;N;N;N;N;N;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;.;.;.;.;N;.;.;N;.;N;.;N;N
REVEL
Uncertain
Sift
Uncertain
D;.;.;.;.;.;.;.;.;.;D;.;.;D;.;D;.;D;D
Sift4G
Benign
T;.;.;.;.;.;.;.;.;.;T;.;.;T;T;T;T;T;T
Polyphen
B;.;B;.;.;.;.;.;.;.;B;.;.;.;.;.;.;.;B
Vest4
MutPred
Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);
MVP
MPC
0.37
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.