rs1309825975
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):āc.15C>Gā(p.Asp5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
SMARCA4
NM_003072.5 missense
NM_003072.5 missense
Scores
8
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.199
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=0.31881338).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SMARCA4 | ENST00000646693.2 | c.15C>G | p.Asp5Glu | missense_variant | Exon 2 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
| SMARCA4 | ENST00000344626.10 | c.15C>G | p.Asp5Glu | missense_variant | Exon 2 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
| SMARCA4 | ENST00000643549.1 | c.15C>G | p.Asp5Glu | missense_variant | Exon 2 of 35 | ENSP00000493975.1 | ||||
| SMARCA4 | ENST00000541122.6 | c.15C>G | p.Asp5Glu | missense_variant | Exon 3 of 35 | 5 | ENSP00000445036.2 | |||
| SMARCA4 | ENST00000643296.1 | c.15C>G | p.Asp5Glu | missense_variant | Exon 2 of 34 | ENSP00000496635.1 | ||||
| SMARCA4 | ENST00000644737.1 | c.15C>G | p.Asp5Glu | missense_variant | Exon 2 of 34 | ENSP00000495548.1 | ||||
| SMARCA4 | ENST00000589677.5 | c.15C>G | p.Asp5Glu | missense_variant | Exon 3 of 35 | 5 | ENSP00000464778.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461312Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726992
GnomAD4 exome
AF:
AC:
1
AN:
1461312
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726992
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;.;.;.;.;T;.;.;.;T;D;.;T;T;T;T;T;T
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
D;.;D;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;D
Vest4
MutPred
Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);Gain of glycosylation at P7 (P = 0.1039);
MVP
MPC
0.24
ClinPred
T
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.