rs267607070
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_001387283.1(SMARCA4):c.3565C>G(p.Arg1189Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Consequence
SMARCA4
NM_001387283.1 missense
NM_001387283.1 missense
Scores
14
3
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.01
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 Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_001387283.1
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SMARCA4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.981
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.3565C>G | p.Arg1189Gly | missense_variant | 26/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.3565C>G | p.Arg1189Gly | missense_variant | 26/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.3565C>G | p.Arg1189Gly | missense_variant | 26/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.3565C>G | p.Arg1189Gly | missense_variant | 26/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;.;D;.;.;.;.;.;.;.;D;.;.;.;.;.;D;D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.;.;H;H;.;H;H;H;H;H;H;H;H;H;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;.;.;.;.;.;.;.;D;.;D;.;D;.;.;D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.;.;.;.;.;.;.;.;D;.;D;.;D;.;.;D;.;.;.
Sift4G
Pathogenic
D;.;.;.;.;.;.;.;.;.;D;.;D;D;D;D;D;D;.;.;.
Polyphen
D;.;D;.;.;.;.;.;.;.;D;.;.;.;.;.;.;D;.;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);Loss of MoRF binding (P = 0.073);.;Loss of MoRF binding (P = 0.073);.;.;.;
MVP
MPC
3.1
ClinPred
D
GERP RS
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.