rs1368858108
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_003072.5(SMARCA4):c.671C>A(p.Ser224*) variant causes a stop gained change. 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. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SMARCA4
NM_003072.5 stop_gained
NM_003072.5 stop_gained
Scores
4
2
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.95
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 Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.671C>A | p.Ser224* | stop_gained | 4/36 | ENST00000646693.2 | NP_001374212.1 | |
SMARCA4 | NM_003072.5 | c.671C>A | p.Ser224* | stop_gained | 4/35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.671C>A | p.Ser224* | stop_gained | 4/36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000344626.10 | c.671C>A | p.Ser224* | stop_gained | 4/35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
SMARCA4 | ENST00000643549.1 | c.671C>A | p.Ser224* | stop_gained | 4/35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000541122.6 | c.671C>A | p.Ser224* | stop_gained | 5/35 | 5 | ENSP00000445036.2 | |||
SMARCA4 | ENST00000643296.1 | c.671C>A | p.Ser224* | stop_gained | 4/34 | ENSP00000496635.1 | ||||
SMARCA4 | ENST00000644737.1 | c.671C>A | p.Ser224* | stop_gained | 4/34 | ENSP00000495548.1 | ||||
SMARCA4 | ENST00000589677.5 | c.671C>A | p.Ser224* | stop_gained | 5/35 | 5 | ENSP00000464778.1 | |||
SMARCA4 | ENST00000643995.1 | c.83C>A | p.Ser28* | stop_gained | 1/32 | ENSP00000496004.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1394426Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 688120
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1394426
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
688120
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.